Morphology of the carotid sinus wall in normotensive and spontaneously hypertensive rats.код для вставкиСкачать
THE ANATOMICAL RECORD 218:426-433 (1987) Morphology of the Carotid Sinus Wall in Normotensive and Spontaneously Hypertensive Rats JOHN T. HANSEN Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642 ABSTRACT The morphology of the carotid sinus region of the internal carotid artery was studied in spontaneously hypertensive rats (SHR) at 5, 8, 16, and 24 weeks of age. The carotid sinus region occupied the proximal millimeter of the internal carotid artery, and was easily recognizable by the presence of a n extensive adventitial capillary plexus, which was absent on adjacent arteries (e.g., common and external carotid arteries). Methylene blue-stained whole-mount preparations showed the extent of baroreceptor nerves over the sinus. Baroreceptor fibers terminated in distinctive bulbous-like endings, which, at the ultrastructural level, were filled with mitochondria. No differences were noted in the sinus adventitial capillary network or baroreceptor distribution between SHR and age-matched Wistar-Kyoto (WKY) normotensive control animals. With the onset of a significant rise in SHR blood pressure, the carotid sinus wall increased in thickness and total vessel size. The w a l l h m e n ratios were significantly larger in the SHR than in age-matched WKY ratios in all age groups. SHR carotid sinus vessel enlargement was uniform throughout the vessel tunics, with no significant change in the proportion of the tunica media occupied by smooth muscle cells. The increase in the carotid sinus wall thickness associated with increasing hypertension could affect the ability of the sinus to distend and may play a secondary role in the maintenance of hypertension by compromising baroreceptor nerve ending sensitivity. The spontaneously hypertensive rat (SHR) is frequently used as a n animal model of human essential hypertension. A number of factors contribute to the development and maintenance of hypertension in this animal, including a variety of neurogenic factors involving both the central and sympathetic nervous systems (Okamoto et al., 1967; Judy et al., 1976), structural alterations in the blood vessels (Warshaw et al., 1980; Lee et al., 1983a), and a loss of baroreceptor reflex control of sympathetic nervous activity (Brown et al., 1978; Judy and Farrell, 1979). Because of the intimate relationship between the baroreceptor nerve endings and carotid sinus wall, any structural alterations that may occur in the sinus wall can alter baroreceptor sensitivity. In fact, several groups have suggested that baroreceptor resetting is due to a reduced vessel distensibility andlor changes in the baroreceptor endings themselves (Andresen et al., 1978; Nosaka and Wang, 1979). In the present study, the morphology of the carotid sinus region of the internal carotid artery was examined in normotensive Wistar-Kyoto (WKY) and SHR rats to determine if alterations in the sinus occurred that might alter normal baroreceptor functioning. 0 1987 ALAN R. LISS, INC. MATERIALS AND METHODS Animals Experiments were performed on male SHR and WKY rats from the Okamoto-Aoki strain obtained from Charles River Breeding Laboratories. Rats were studied a t 5,8,16, and 24 weeks of age. All animals were housed in animal rooms on a 14:lO LD cycle with temperature maintained a t 75 2°F at 50% relative humidity. Systolic blood pressure was determined in conscious rats by a photoelectric tail cuff pulse detector (IITC, Inc., Landing, NJ). Animals were conditioned to the restraining cages prior to pressure measurements, and mean systolic pressure was determined from 4 or 5 pressure measurements. Systolic blood pressures were obtained on the afternoon of the day before sacrifice. Vascular Casts Three to five SHR and WKY rats at each age interval (5, 8, 16, and 24 weeks) were anesthetized with sodium Received November 26, 1986; accepted March 6, 1987 CAROTID SINUS WALL IN HYPERTENSION pentobarbital (40 m g k g i.p.1 and perfused through the heart with warm (30°C) saline containing 1,000 units of heparin per 500 ml. Perfusion pressure was maintained a t 80% of the mean systolic blood pressure (Hart et al., 1980) by adjusting the height of the fluid bottles in our gravity perfusion system. When the effluent from the incised right atrium was clear (about 30-60 sec), the rats were perfused with a warm (30°C) fixative solution containing 3% glutaraldehyde in 0.1 M sodium phosphate buffer a t pH 7.2. Each animal was infused with 200 ml of fixative. Immediately following the perfusion, Mercox (Ladd Research Industries, Burlington, VT) was prepared by combining 20 ml of resin with 1 ml of catalyst in a 50-ml syringe. Mercox is a low-viscosity methacrylate resin used for preparing corrosion casts of the vasculature. The Mercox mixture was infused through the heart and into the ascending aorta in 1min, by which time the resin had begun to polymerize. The infused rat was cured for 1 h r in a n oven at 50°C, and then the desired area of the carotid bifurcation was removed. These samples were macerated in 5.25% hypochlorite (household bleach) for 24-48 hr. Once clean of soft tissue, the casts were rinsed in distilled water, airdried, oriented, and mounted on scanning electron microscopy stubs, sputter-coated with gold, and examined in a scanning electron microscope at 15 kV. Appropriate casts were photographed on Polaroid Type 55 film (ASA 50). Methylene Blue Staining The distribution of the carotid sinus baroreceptor nerves over the carotid sinus region of the internal carotid artery was studied in whole-mount preparations stained with methylene blue (Richardson, 1969; McDonald, 1983). Five or six WKY and SHR rats at 5, 8, and 16 weeks of age were studied. The rats were anesthetized with sodium pentobarbital (40 m g k g i.p.) and injected intravenously with heparin (250 units). Then the rats were perfused with 0.9% NaCl via the left ventricle for 1min at 120 mm Hg, followed by 1 liter of 0.01% methylene blue chloride in phosphate buffer at pH 5.0 for 10 min. Prior to the perfusion, the methylene blue chloride solution was equilibrated with 100% 0 2 by bubbling the oxygen through the solution. When the perfusion was finished, the carotid bifurcations were removed immediately and immersed in ammonium molybdate fixative at 4°C for 6-24 hr (Richardson, 1969). Specimens consisting of the carotid sinus, carotid body, and superior cervical ganglion were rinsed in water, flattened between two glass slides in 100% methanol, dehydrated in methanol, cleared in xylene, mounted as whole mounts on slides, and coverslipped with Permount. The linear extent of the carotid sinus nerve innervation from caudal to rostra1 on the sinus portion of the internal carotid artery was measured in the light microscope a t 40 x with a n ocular reticule. Light and Electron Microscopy WKY and SHR rats at each age interval were anesthetized with sodium pentobarbital(40 m g k g i.p.1 and their carotid bifurcations (4 to 6 bifurcations per age group) were fixed for light and electron microscopy by intracardiac perfusion of a solution containing 3% glutaraldehyde in 0.076 M cacodylate buffer with 60 mM H202, 2 mM CaC12, 30 mM sucrose, and 1 mM polyvinylpyroli- 427 done (pH 7.2, room temperature, 520 mOsmol). The fixative was preceded by a saline flush (50 ml), and pressure was controlled by gravity a t 80% of the mean systolic pressure (Hart et al., 1980). Subsequent morphological examination verified that all vessels were fixed in a fully dilated (relaxed) state, as evidenced by the stretched internal elastic lamina, rounded smooth muscle cell nuclei, and smooth plasma membrane, typical of relaxed smooth muscle cells. Following a 10-min perfusion, the carotid bifurcation was removed and immersed in fresh fixative for a n additional 4-6 h r at 4°C. The carotid sinus region of the proximal internal carotid artery was sectioned transversely into a small piece about 1 mm long and washed in cacodylate buffer overnight. The tissue samples were postfixed in 1.5%osmium tetroxide in 14 mM Verona1 acetate-HC1 buffer (pH 7.4) for 1 hr a t room temperature. The samples were then stained en bloc with 1.5%uranyl acetate in 25 mM maleate buffer (pH 5.0) for 6 h r a t room temperature, dehydrated in acetone, and embedded flat in Spurr's plastic in aluminum weighing pans. The specimens then were sawed from disks of the polymerized resin, oriented, and mounted on transparent acrylic cylinders (7.9 mm x 12.7 mm) with cyanoacrylate adhesive. Sinus regions were oriented so that sections could be cut transversely across the vessel. For light microscope examination, 1-pm sections were cut from the center of the sinus and stained with toluidine blue. These sections were coverslipped and photographed in the light microscope. For electron microscopy, thin sections (70 nm) were cut with a diamond knife on a n ultramicrotome, and collected on 50-mesh formvarcarbon-coated grids. Thin sections were stained on grid with lead citrate and examined in the electron microscope at 60 kV. Morphometric Analysis For light microscope analysis, 1-pm plastic sections were photographed and enlarged on photographic paper . standard morphometric apto either x 140 or ~ 2 0 0By proaches (Weibel, 1979), each carotid sinus was measured on a Zeiss MOP-3 digitizing pad (Car1 Zeiss, Inc., New York, NY) and the data were recorded. The prints were coded so that the observer collecting the data was unaware of group identity. Estimates of wall thickness (collected at 12 equidistant points around each vessel), vessel perimeter and area (tunica intima and media), and lumen perimeter and area were collected directly by tracing over the structures with the digital image analyzer. Significant differences between age-matched WKY and SHR samples were determined by a Student t test. A probability of P<O.O5 was chosen as the level of significance. At the ultrastructural level, morphometric data on the baroreceptor nerve endings were not collected, although their general features are described in Results. Morphometric data were collected on the features of the carotid sinus wall. Each of four or five carotid sinus samples from each group of rats was photographed across the entire thickness at two different locations. The first complete sections encountered in the electron microscope were used for sampling. Micrographs were taken a t low magnifications ( x 2,000) and photographically enlarged to ~ 5 , 0 0 0The . fractional volume Wv) of smooth muscle cells and the extracellular compartment (largely colla- 428 J.T. HANSEN gen and elastic components) were estimated by pointcounting techniques (Weibel, 1979). A transparent overlay with 63 points was used to collect the data from each 8-in x 10-in print. The data were pooled from each sinus and the values averaged to determine a group average. Data were expressed as percentage of the tunica media occupied by smooth muscle or the extracellular compartment. Significant differences between age-matched WKY and SHR samples were determined by a n ANOVA. A probability of P< 0.05 was chosen as the level of significance. RESULTS The mean systolic blood pressures and body weights a t the time of sacrifice of the WKY and SHR groups a t 5 , 8, 16, and 24 weeks of age are shown in Table 1. The mean systolic blood pressure in the SHR was already significantly elevated a t 5 weeks of age compared to the age-matched WKY animals. From 16 weeks of age and older, the SHR body weight was significantly greater (P<O.OOl) than that of the normotensive WKY rats. TABLE 1. Mean systolic blood pressure and body weight' Group WKY-5 SHR-5 P WKY-8 SHR-8 P WKY-16 SHR-16 P WKY-24 SHR-24 P Body weight (gm) Blood pressure (mm Hg) 111.6 f 20.5 129.4 f 15.8 0.02 117.8 f 11.3 136.7 f 8.7 0.001 116.9 f 8.9 150.8 f 26.1 0.001 107.8 f 8.9 164.2 f 24.4 0.001 N 86.5 f 10.9 74.4 f 11.1 0.01 180.9 f 15.6 174.4 f 20.1 NS 242.4 f 9.5 304.8 k 10.4 0.001 289.8 f 8.1 372.1 f 7.0 0.001 15 14 16 15 16 15 6 6 'Values are means k standard deviations of each group of 5, 8, 16, and 24 weeks of age. P values compare WKY rats with their agematched SHR. General Morphology The carotid sinus region in both WKY and SHR occupied the proximal millimeter of the internal carotid artery. The distal common carotid artery was a transitional artery (Simionescu and Simionescu, 1983), which displayed both prominent elastic lamellae and well-defined bands of smooth muscle (Fig. 1). Although the elastic lamellae appeared thinner than those of the common carotid artery, the proximal portions of the external and internal carotid arteries also were transitional arteries, that is, they possessed histological features intermediate between elastic and muscular arteries (Figs. 2 and 3). The carotid sinus in the WKY and SHR was easily recognizable by the presence of a capillary plexus in its tunica adventitia (Figs. 3 and 4). The capillaries were not observed penetrating the tunica media, so the identification of this adventitial network as true vasa vasorum is questionable. No other region of the adjacent common, external, or internal carotid arteries possessed this capillary network. This adventitial, or perivascular, network of capillaries appeared to originate from small arterioles of the adjacent carotid body chemoreceptor (Fig. 4). Several larger venules also were present and presumably drained the carotid body and sinus capillaries. Baroreceptor Morphology The carotid sinus region also was fairly well delineated in methylene blue-stained whole-mount preparations. Nerve axons were observed over the entire extent of the sinus region but were most abundant over the dorsolateral aspect of the sinus. These presumptive baroreceptor fibers terminated in bulbous endings when stained with methylene blue (Figs. 5 and 6). Often, one or two axons gave rise to several secondary branches that terminated upon the sinus wall in typical bulbous profiles (Fig. 6). Some of these axon profiles were quite convoluted or coiled in appearance. The precise number of carotid sinus axons terminating on the sinus wall could not be determined because the proportion of axons stained by methylene blue was not known. If any differ- TABLE 2. Light microscoDe measurements of the carotid sinus' 5 Week Wall thickness 8 Week WKY SHR 45.1 f 2 42.1 f 2 WKY SHR 16 Week SHR WKY 40.3 f 1.5 50.0 f 1.72 40.2 f 2 54.3 24 Week SHR WKY 2.62 47.9 f 2.4 62.8 f 1.72 (pm) Vessel perimeter (10~ pm) Vessel area (104 pm2) Lumen perimeter (10~ pm) Lumen area (104pm2) 21.9 f 0.8 18.4 f 0.72 23.5 f 0.4 23.7 k 0.4 25.0 f 0.9 30.4 f 1.02 23.1 f 0.7 29.4 f 0.72 37.2 f 2.5 25.8 f 1.9' 42.4 f 1.4 42.9 f 1.1 47.8 f 3.3 71.8 19.2 f 0.8 16.0 f 0.6 21.1 f 0.4 20.7 k 0.4 22.5 k 0.9 27.0 k 0.g2 20.2 f 0.6 25.6 f 0.7' 28.5 f 2.2 18.9 f 1.5 33.9 f 1.2 32.4 f 0.9 38.6 f 2.6 56.5 f 3.42 31.3 f 1.9 51.0 k 2.62 Total vessel Derimeter 23.9 f 0.9 20.1 k 0.8 26.1 f 0.6 25.8 f 0.4 27.4 k 1.0 32.8 f 1.12 25.5 f 0.8 32.4 f 0.82 4.62 41.3 f 2.5 67.5 k 3.12 (10' pm) Wallflumen ratio3 77.9 f 2.5 97.8 f 4.82 67.4 f 2.0 82.3 f 2.2' (1n-3) 'Values are means standard error of the mean. 'P < 0.01, significantly greater than age-matched WKY. 3Wall thicknessflumen diameter. 58.8 k 1.9 70.5 f 2.62 74.1 f 2.1 87.5 f 2.2' CAROTID SINUS WALL IN HYPERTENSION 429 Fig. 1. Light micrograph of distal common carotid artery showing a portion of the lumen and alternating bands of smooth muscle and elastic lamellae (el). ~ 2 2 0 . h Fig. 2. Micrograph of a portion of the wall of the proximal external carotid artery. The elastic lamellae are less distinct. x220. be A ..- A B 5Oum Fig. 3. Micrograph of a portion of the carotid sinus wall from a 16week-old WKY. Note elastic lamellae and smooth muscle cells of tunica media. A portion of the adjacent carotid body (cb) chemoreceptor also is visible. ~ 2 2 0 . Fig. 4. Scanning electron micrograph showing proximal portions of the external (ec) and internal (ic) carotid arteries. Note the distinctive adventitial capillary network (cn) over the proximal internal carotid artery, demarcating the carotid sinus zone. These capillaries appear to come from the vascular network of the adjacent carotid body. Several venules (v) also are evident in this micrograph. x 75. Fig. 5. Light micrograph of several presumptive baroreceptor endings of the carotid sinus stained with methylene blue. Note their bulbous endings and coiled appearance. From a 5-week-old SHR sinus. x290. Fig. 6. Camera lucida drawings of two methylene blue-stained wholemount preparations of presumptive baroreceptor nerve endings. Often, one or two axons give rise to several secondary branches that are coiled and terminate in bulbous endings. 430 J.T.HANSEN TABLE 3. Fractional volume of tunica media occupied by smooth muscle and extracellular components’ Smooth muscle Group WKY-5 SHR-5 WKY-8 SHRS WKY-16 SHR-16 WKY-24 SHR-24 (%I 45.9 36.7 41.6 39.2 36.9 34.2 41.1 41.0 k 0.5 * 1.4 *k 7.9 1.6 f 3.2 k 4.1 f 6.7 f 2.6 Extracellular components’ (%) N 54.2 f 0.4 63.3 k 1.3 58.4 f 1.4 60.8 f 6.8 63.1 f 2.9 65.8 f 3.6 58.9 f 6.0 59.0 k 2.3 4 5 4 4 5 5 5 5 ‘Values are means standard error of the mean. There were no significant differences (ANOVA). ‘Includes elastic laminae and collagen. ences in the number or distribution of axons did exist among the WKY and SHR groups, they were not evident in these whole-mount preparations. Ultrastructurally, the presumptive baroreceptor endings of the carotid sinus nerve were quite distinct. Most axon terminals were located in the medial one third of the tunica adventitia and possessed a n axoplasm almost completely filled with round or oval mitochondria (Figs. 7-9). The mitochondria-filled bulbous terminals were partially or completely surrounded by Schwann cell processes and were found within a bed of extracellular connective tissue composed largely of collagen fibers (Figs. 8, 9). Microtubules, a few dense-core vesicles, and larger dense bodies (perhaps lysosomes?) also were present in the terminals (Fig. 8).Occasionally, multiple layers of the basal lamina were observed surrounding each terminal (Fig. 10). This feature was inconsistent, but it appeared in both WKY and SHR carotid sinus samples. Presumptive baroreceptor terminals were never observed in the tunica media or adjacent to smooth muscle cells. Obvious morphological differences between the axon terminals of WKY and SHR carotid sinuses were not noted. Analysis of the Carotid Sinus Wall Morphometric data gathered at the light microscope level from the carotid sinus region are summarized in Table 2. The wall thickness (tunica intima, media, and adventitia) was significantly greater (P< 0.01) in the SHR from 8 to 24 weeks of age. The carotid sinus portion of the internal carotid artery in the SHR was significantly larger (P< 0.01) (vessel perimeter and area) at 16 and 24 weeks of age compared to the age-matched WKY. Lumen perimeter and area also were larger in the SHR a t 16 and 24 weeks. Across the various SHR age groups from 5 to 16 weeks, there was a tendency for the wall thickness, vessel perimeter and area, lumen perimeter and area, and total vessel perimeter to increase. While these same parameters increased in the WKY carotid sinuses, their magnitude was much smaller. For example, vessel area and lumen area increased 162% and 170%, respectively, in the SHR from 5 to 24 weeks of age. Over the same period, vessel area and lumen area were increased only 11%and 10%, respectively, in the WKY. Likewise, wall thickness increased 49% in the SHR, but only 6% in the WKY. The wallAumen ratio of the carotid sinus region was significantly larger in the SHR in all age groups. At the ultrastructural level, the fractional volume of the tunica media occupied by smooth muscle and extracellular components (elastic lamellae and collagen) was determined. These data are shown in Table 3. The percentage of the tunica media occupied by smooth muscle cells tended to increase from a low of 36.7% a t 5 weeks of age to a high of 41% at 24 weeks of age in the SHR carotid sinus wall. However, this tendency was not significantly different from the age-matched WKY smooth muscle fractional volume in any age group (Table 3). DISCUSSION The salient findings of the present investigation are that the carotid sinus baroreceptor distribution and morphology in WKY and SHR rats are similar, but the carotid sinus wall in the SHR is significantly thicker. This increase in thickness probably is secondary to the increase in blood pressure. Morphologically, the carotid sinus portion of the proximal internal carotid artery is a transitional artery, possessing histological characteristics intermediate between elastic and muscular arteries. The sinus region in both the WKY and SHR, unlike the adjacent portions of the common, internal, or external carotid arteries, possesses a rich perivascular network of capillaries in its tunica adventitia. McDonald and Larue (1983) have described this unique feature of the carotid sinus in rats of the Long-Evans strain and refer to this capillary network as vasa vasorum. However, unlike true vasa vasorum, which penetrates the tunica media, this “adventitial” network of capillaries is never observed branching the media. The capillary network appears to originate from small arterioles of the adjacent carotid body, and accompanies branches of the carotid sinus nerve and sympathetic fibers as they pass over the sinus region. Baroreceptor nerve endings usually are observed within the immediate vicinity of the capillaries, and they may receive their blood supply through this network (McDonald and Larue, 1983; Hansen, 1985). No obvious differences in the capillary network are evident between the WKY and SHR carotid sinuses. From methylene blue-stained preparations, it is clear that the baroreceptive field encompasses the most proximal millimeter of the internal carotid artery wall. Baroreceptor endings are most prominent over the dorsolateral aspect of the sinus. A similar pattern of distribution exists in the Long-Evans rat (McDonald, 1983). Yates and Chen (1980) described the baroreceptor field as limited to a narrow area of about 0.5 mm wide and covering one third to one half of the circumference of the internal carotid artery. With methylene blue staining one is able to examine the entire sinus in a wholemount preparation; by this approach, presumptive baroreceptor endings are observed over a broader area of the sinus wall, although by far the greatest accumulation of endings lies on the dorsolateral aspect of the artery. The distribution in the WKY and SHR is similar. Baroreceptor nerve endings exhibit a unique bulbous appearance in methylene blue-stained preparations (McDonald, 1983) that a t the ultrastructural level appear as mitochondria-packed terminals. These characteristic features are common to baroreceptor endings described by others in a variety of species (Rees, 1967; CAROTID SINUS WALL IN HYPERTENSION Fig. 7.Electron micrograph of several presumptive baroreceptor endings (b)situated in the medial one third of the tunica adventitia. Note the adjacent external elastic lamina (ell separating the tunica adventitia from the tunica media. Baroreceptor endings often are surrounded by processes of Schwann cells (S).Sinus wall of a 24-week-old SHR. ~ 3 , 2 6 0 . Fig. 8.Several baroreceptor endings in the sinus wall of a 24-weekold SHR. Note that the endings are filled with round or oval mitochondria and are surrounded by processes of a Schwann cell. Occasional dense-core vesicles (dcv) and larger dense bodies resembling lysosomes (lys) are present in the terminals. Collagen (col) and elastic fibers (ef) fill the extracellular spaces. x 18,000. 431 Fig. 9.Baroreceptor ending from a n 8-week-old WKY carotid sinus. Note several dense-core vesicles (dcv) and numerous mitochondria. Collagen (col) lies in the extracellular space, and the ending is enveloped by a Schwann cell process (arrows). ~21,400. Fig. 10. Portion of baroreceptor preterminal axon in longitudinal section exhibiting microtubules (mt), and partially surrounded by a Schwann cell process. Note multiple layers of basal lamina (bl). From a n 8-week-old WKY sinus. ~29,750. 432 J.T. HANSEN Bock and Gorgas, 1976; Knoche and Addicks, 1976; Krauhs, 1979; Knoche et al., 1980; Yates and Chen, 1980; Taha et al., 1983). The baroreceptor endings in the WKY and SHR are similar in appearance. The nerve endings are never observed in the tunica media, but are limited to the inner portions of the tunica adventitia in close association with collagen and elastic fragments. Bock and Gorgas (1976) interpret the large number of mitochondria in the terminals as indicative of a high metabolic rate, such as may be required by mechanoreceptors a s they respond to pressure changes. A basal lamina surrounds the receptors and their Schwann cells and is prominent, extensive, and multilayered in the rat carotid sinus (Yates and Chen, 1980) and aortic baroreceptors (Krauhs, 1979).The significance of this multilayered basal lamina is unclear, although Yates and Chen (1980) suggest that Schwann cells andor nerve terminals may lay down additional basal laminae in response to the increase in wall tension during progressive hypertension. In this study, multilayered basal laminae, although not ubiquitous, are present in both WKY and SHR sinus baroreceptors, regardless of blood pressure. Moreover, Krauhs (1979) describes similar multiple layers of basal lamina in WKY and SHR aortic baroreceptors, irrespective of blood pressure. Therefore, this feature may be a general characteristic of rat baroreceptors. With the onset of a significant rise in SHR blood pressure, the carotid sinus wall increases in thickness,-concomitantly with a significant increase in total vessel size. Most importantly, however, the wall/lumen ratios are significantly larger in the SHR than in age-matched WKY ratios in all age groups. This increase appears to be uniform throughout the vessel wall of the SHR, since ultrastructural analysis shows that the proportion of the tunica media occupied by smooth muscle does not vary significantly between the age-matched WKY and SHR groups. However, this enlargement of the sinus wall differs from the pattern observed on other SHR vessels. Jurokova et al. (1976) demonstrated smooth muscle hypertrophy and hyperplasia in the aorta of rats with short-term (3-6 months) and long-term (12-16 months) spontaneous hypertension. Likewise, alterations are present in mesenteric vessels, involving the muscular and arteriolar vessels but not the elastic (superior mesenteric) ones (Warshaw et al., 1979; Lee et al., 1983a, 198313). The reaction of the carotid sinus wall to hypertension may be a result of its elastic and muscular morphology, not being either a truly elastic or muscular (resistance) vessel. Additional studies of other transitional arteries are needed to resolve this possibility. Thickening of the carotid sinus wall, as observed in this study, is dramatic, accounting for a 49% increase between 5 and 24 weeks in the SHR, whereas the WKY sinus wall increases in thickness by only 6%. One hypothesis of baroreceptor function suggests that the distensibility of the carotid sinus wall results in a mechanical deformation that elicits a mechano-electrical action on baroreceptor nerve endings (Brown, 1980). The resultant depolarization of the baroreceptors then is transmitted to the central nervous system via carotid sinus nerve afferents. The elastic properties of the carotid sinus wall permit this distensibility. One might speculate that a n increase in sinus wall thickness could compromise this mechano-electrical interaction, and result in a decrease in baroreceptor sensitivity. The increase in wall thickness probably is secondary to some other central andor peripheral abnormality in the SHR that precipitates the increase in blood pressure. Nevertheless, once hypertension is manifest, a n increasingly thicker carotid sinus wall may exacerbate the hypertension further by compromising baroreceptor sensitivity. ACKNOWLEDGMENTS I thank Norma Peche, Albert Guzman, and Andrew Howell for their excellent technical assistance. This study was supported by National Institutes of Health grant HL36038, and a Research Career Development Award. LITERATURE CITED Andresen, M.C., J.M. Krauhs, and A.M. Brown (1978)Relationship of aortic wall and baroreceptor properties during development in normotensive and spontaneously hypertensive rats. Circ. Res., 43~728738. Bock, P., and K. Gorgas (1976)Fine structure of baroreceptor terminals in the carotid sinus of guinea pigs and mice. Cell Tissue Res., 170~95-112. Brown, A. (1980) Receptors under pressure. An update on baroreceptors. Circ. Res., 46:l-10. Brown, A.M., W.R. Saum, and S.Yasui (1978) Baroreceptor dynamics and their relationship to afferent fiber type and hypertension. Circ. Res., 42:694-702. Hansen, J.T. (1985) Can arterial chemoreceptors influence baroreceptors? Soc. Neurosci. Abstr., 11~196. Hart, M.N., D.D. Heistad, and M.J. Brody (1980) Effect of chronic hypertension and sympathetic denervation on wallflumen ratio of cerebral vessels. Hypertension, 2~419-423. Judy, W.V., and S.K. Farrell(1979) Arterial baroreceptor reflex control of sympathetic nerve activity in the spontaneously hypertensive rat. Hypertension, 1:605-614. Judy, W.V.,A.M. Watanabe, D.P. Henry,H.R. Besch, Jr., W.R. Murphy, and H. Haskel (1976) Svmuathetic nerve activity: Role in the regulation of blood pressure i n the spontaneously-hypertensive rat. Circ. Res., 38/Suppl. 2):21-29. .Jurokova, Z., P. Hadjisky, J. Renais, and L. Scebat (1976)Aortic smooth muscle cells reaction in rat spontaneous hypertension. Pathol. Eur., 11:105-115. Knoche, H., and K. Addicks (1976)Electron microscopic studies of the pressoreceptor fields of the carotid sinus of the dog. Cell Tissue Res., 173:77-94. Knoche, H., L. Wiesner-Menzel, and K. Addicks (1980)Ultrastructure of haroreceptors in the carotid sinus of the rabbit. Acta Anat., 106~63-83. Krauhs, J. (1979) Structure of rat aortic baroreceptors and their relationship to connective tissue. J. Neurocytol., 8~401-414. Lee, R.M.K.W., J.B. Forrest, R.E. Garfield, and E.E. Daniel (1983a) Ultrastructural changes in mesenteric arteries from spontaneously hypertensive rats. Blood Vessels, 20~72-91. Lee, R.M.K.W., R.E. Garfield, J.B. Forrest, and E.E. Daniel (1983b) Morphometric study of structural changes in the mesenteric blood vessels of spontaneously hypertensive rats. Blood Vessels, 20:5771. McDonald, D.M. (1983) Morphology of the rat carotid sinus nerve. I. Course, connections, dimensions and ultrastructure. J. Neurocytol., 12~345-372. McDonald, D.M., and D.T. Larue (1983)The ultrastructure and connections of blood vessels supplying the rat carotid body and carotid sinus. J. Neurocytol., 12:117-153. Nosaka, S., and S.C. Wang (1979)Carotid sinus baroreceptor functions in the spontaneously hypertensive rat. Am. J. Physiol., 222:10791084. Okamoto, K., S. Nosaka, Y. Yamori, and M. Matsumoto (1967)Partici- CAROTID SINUS WALL IN HYPERTENSION pation of neural factors in the pathogenesis of hypertension in the spontaneously hypertensive rat. Jpn. Heart J., 8:168-180. Rees, P.M. (1967) Observations on the fine structure and distribution of presumptive baroreceptor nerves at the carotid sinus. J. Comp. Neurol ., I31:517-548. Richardson, K.C. (1969) The fine structure of autonomic nerves after vital staining with methylene blue. Anat. Rec., 164:359-378. Simionescu, N., and M. Simionescu (1983) The cardiovascular system. In: Histology. L. Weiss, ed. Elsevier Biomedical, New York, pp. 371-433. Taha, A.A.M., E.M. Abdel-Magied, and A.S. King (1983) Ultrastructure of aortic and pulmonary baroreceptors in the domestic fowl. J. Anat., 137:197-207. 433 Warshaw, D.M., M.J. Mulvany, and W. Halpern (1979) Mechanical and morphological properties of arterial resistance vessels in young and old spontaneously hypertensive rats. Circ. Res., 45:250-259. Warshaw, D.M., D.T. Root, and W. Halpern (1980) Effects of antihypertensive drug therapy on the morphology and mechanics of resistance arteries from spontaneously hypertensive rats. Blood Vessels, 17:257-270. Weibel, E.R. (1979) Stereological Methods, Vol. 1: Practical Methods for Biological Morphometry. Academic, New York, pp. 63-161. Yates, R.D., and I.L. Chen (1980) An electron microscopic study of the baroreceptors in the internal carotid artery of the spontaneously hypertensive rat. Cell Tissue Res., 205473-483.