Increases in renal angiotensin II content and tubular angiotensin II receptors in prehypertensive spontaneously hypertensive rats

To examine the role of the intrarenal renin-angiotensin system in the development of hypertension in spontaneously hypertensive rats (SHR), we measured angiotensin II contents and tubular 125I-angiotensin II binding sites in the kidney of SHR and age-matched Wistar-Kyoto rats (WKY). In prehypertensive (4-week-old) SHR, not only the kidney angiotensin II content but also the angiotensin II receptor density in brush border membranes were significantly higher than in the WKY. In contrast, angiotensin II levels in the 20-week-old SHR kidneys were significantly lower than in the WKY. Acceleration of the intrarenal renin-angiotensin system and the increased density of tubular angiotensin II receptors in young SHR may therefore play an important role in the development of high blood pressure in SHR.     

Altered expression of BK channel beta1 subunit in vascular tissues from spontaneously hypertensive rats

Correlation of blood pressure (BP) with expression levels of large-conductance, voltage- and Ca2+-activated K+ (BK) channel beta1 subunit in vascular tissues from spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD) at different ages was investigated. Systolic BP and BK beta1 expression in mesenteric arteries at either mRNA or protein levels were not different among 4-week-old SHR, WKY, and SD. With hypertension developed at 7 weeks and reached plateau at 12 weeks, expression levels of BK beta1 mRNA in mesenteric arteries and aortae from SHR during this period of time were significantly higher than in age-matched normotensive WKY. The BK beta1 protein expression was significantly higher in mesenteric arteries from 12-week-old but not 7-week-old SHR when compared with age-matched WKY and SD. The BK beta1 protein levels in aortae were not different among 7-week-old SHR, WKY, and SD but were significantly lower in 12-week-old WKY than in age-matched SHR and SD. Captopril treatment normalized BP of 12-week-old SHR. This treatment downregulated BK beta1 protein in mesenteric arteries but upregulated it in aortae. No significant difference in BK alpha subunit expression was detected in mesenteric arteries from three strains of rats as well as the captopril-treated SHR. It appears that expression patterns of BK beta1 in vascular tissues vary depending on tissue types, animal age, and animal strains. Expression of BK beta1 in mesenteric arteries is closely correlated with BP in SHR. Increased BK beta1 expression in mesenteric arteries may represent a compensatory reaction to limit the development of hypertension.     

Increased concentration of angiotensin II binding sites in selected brain areas of spontaneously hypertensive rats

We studied the density of the angiotensin II (Ang II) binding site in discrete brain nuclei of 4-week-old and 14-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto (WKY) control rats by autoradiographic binding techniques. Tissue sections were incubated in vitro with 3 nmol/l [125I]Sar1Ang and results were analysed by computerized microdensitometry and by comparison with 125I-standards. Both young and adult SHR (aged 4 and 14 weeks, respectively) had significantly higher Ang II binding site concentrations in the median preoptic nucleus (MPO), subfornical organ (SFO), paraventricular nucleus (PVN) and nucleus of the solitary tract (NTS) when compared to age-matched WKY control rats. No significant difference was found between strains in other brain areas such as the olfactory bulb, suprachiasmatic nucleus (SCh), inferior olive (IO) and area postrema (AP). It was observed that the concentration of Ang II binding sites increased with age in PVN of both SHR and WKY, while the number of binding sites in the MPO and IO decreased with age. In SHR, alteration in Ang II binding is restricted to brain nuclei involved in the central pressor action of Ang II and seems to be related to the development and maintenance of spontaneous hypertension.     

Altered angiotensin II-induced small artery contraction during the development of hypertension in spontaneously hypertensive rats.

This study assessed whether the angiotensin-II (Ang II)-induced contractile responsiveness of resistance arteries is altered during the development of hypertension in spontaneously hypertensive rats (SHR). Structural parameters and Ang II-stimulated contraction were determined in small mesenteric arteries from 6-week-old (phase of developing hypertension) and 21-week-old SHR (phase of established hypertension), compared with age-matched Wistar-Kyoto rats (WKY). To ascertain whether effects were specific for Ang II, contractile responses to another vasoactive agonist, vasopressin (AVP), were also determined. Systolic blood pressure was measured in conscious rats by the tail-cuff method. Segments of third-order mesenteric arteries (approximately 200 microm in diameter and 2 mm in length) were mounted in a pressurized system with the intraluminal pressure maintained at 45 mm Hg. Blood pressure was significantly increased in SHR (P < .001) and was higher in adult than in young SHR (P < .001). Ang II dose-dependently increased contraction, with responses significantly greater (P < .05) in SHR than in age-matched WKY. SHR, in the early phase of hypertension, exhibited significantly augmented contractile responses (Emax = 70 +/- 5%), compared with SHR with established hypertension (Emax = 33 +/- 5%). These effects were not generalized, as responses to AVP were not significantly different between young and adult SHR. Functional Ang II-elicited alterations were associated with structural modifications: 6-week-old SHR had smaller media to lumen ratio compared with 21-week-old SHR (8.1% +/- 0.17% v 10.6% +/- 0.20%, P < .01). In young SHR vessels the media cross-sectional area was unchanged relative to age-matched WKY rats, suggesting eutrophic remodeling (remodeling index 101.4% v 93.3% young v adult), whereas the cross-sectional area of adult vessels was increased in comparison to WKY rats, suggesting mild hypertrophic remodeling (growth index -1.0% v 15.2%, young v adult). In conclusion, the present study demonstrates that in SHR with early hypertension and slight medial thickening, Ang II-mediated vascular contractile responsiveness is significantly augmented compared with SHR with established hypertension and more severe vascular structural changes. These findings indicate attenuation, as hypertension progresses, of the initially enhanced vascular reactivity to Ang II that is present during the development of hypertension in SHR.     

A comparison of CNS angiotensin II binding in the hypothalamus-thalamus-septum-midbrain region of developing spontaneously hypertensive and normotensive rats

Specific angiotensin II (ANG II) binding was studied in brain homogenates from the hypothalamus-thalamus-septum-midbrain (HTSM) region of age-matched 4-, 8-, 12- and 16-week spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using 125I-angiotensin II. Scatchard analysis revealed that the dissociation constants (Kd) ranged from 0.36 to 0.73 nmol/l, although these values were not significantly different at any given age period between the SHR and WKY rats. In contrast, a statistically significant increase in ANG II receptor binding was seen between the SHR and WKY rat at 4 weeks of age. However, this difference was not observed at older age periods. Furthermore, both the SHR and WKY rat showed a decrease in ANG II receptor levels during development, with the most marked reductions occurring between 12 and 16 weeks of age for both strains. These findings suggest that ANG II receptors in the HTSM region of both the SHR and WKY rat are down-regulated during development, that receptor loss is more significant in the SHR than in its normotensive control and that binding capacity differences between the two strains are only seen before the onset of measureable increases in the arterial pressure of the SHR. We conclude that there is a significant difference in the ANG II binding capacity during the development of hypertension in the SHR as compared with the WKY rat and therefore it may play a role in the pathogenesis of this disorder.     

Age-related decrease of calcitonin gene-related peptide-containing vasodilator innervation in the mesenteric resistance vessel of the spontaneously hypertensive rat

We previously demonstrated that the mesenteric resistance blood vessels have nonadrenergic, noncholinergic vasodilator innervation in which calcitonin gene-related peptide (CGRP) is a possible neurotransmitter. The role of CGRP-containing vasodilator nerves in hypertension was investigated in perfused mesenteric vascular beds isolated from spontaneously hypertensive rats (SHR). The adrenergic vasoconstrictor responses to perivascular nerve stimulation in both SHR (8-, 15-, and 30-week-old) and age-matched Wistar-Kyoto (WKY) rat preparations increased with aging, but the response was greater in SHR than in WKY rats at all ages. The preparation isolated from SHR and WKY rats was precontracted by continuous perfusion of Krebs' solution containing 7 x 10(-6) M methoxamine plus 5 x 10(-6) M guanethidine. In both SHR and WKY rats, perivascular nerve stimulation (1-8 Hz) produced frequency-dependent vasodilation, which was blocked by 1 x 10(-7) M tetrodotoxin, pretreatment with 5 x 10(-7) M capsaicin, and denervation by cold storage (4 degrees C for 72 hours). The vasodilation induced by perivascular nerve stimulation in SHR greatly decreased with age, whereas a slight decrease in the response with age was found in WKY rats. The neurogenic vasodilation in the young SHR preparation was similar in magnitude to the vasodilation in age-matched WKY rats, whereas the vasodilation in 15- and 30-week-old SHR was significantly smaller than that in age-matched WKY rats. In both SHR and WKY rats, perfusion of rat CGRP (1 x 10(-10) to 3 x 10(-8) M) produced marked vasodilation in a concentration-dependent manner. The CGRP-induced vasodilation in SHR increased with age, whereas an age-related decrease in vasodilation was found in WKY rats. Perivascular nerve stimulation (4 and 8 Hz) of the perfused mesenteric vascular bed evoked an increased release of CGRP-like immunoreactive substance in the perfusate, which was significantly less in 15-week-old SHR than in age-matched WKY rats. Immunohistochemical studies showed an age-related decrease in CGRP-like immunoreactive fibers in SHR but not in WKY rats. These results suggest that CGRP-containing vasodilator innervation is greatly decreased when SHR develop and maintain hypertension. It is also suggested that the decreased vasodilator mechanism by CGRP-containing nerves contributes to the development and maintenance of hypertension.     

Reduced calcium sensitivity of dihydropyridine binding to calcium channels in spontaneously hypertensive rats.

To explore the role of calcium channels in hypertension, dihydropyridine ([3H]PN200-110) binding to heart, brain, and skeletal muscle microsomes of 4-, 8- and 15-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats was measured. At a constant Ca2+ ion concentration (pCa 3.0), maximal binding (Bmax) of dihydropyridine binding to heart and brain microsomes was significantly enhanced in 8- and 15-week-old SHR compared with WKY rats (p less than 0.01), whereas this phenomenon was not observed in 4-week-old SHR and WKY rats. Bmax and dissociation constant (Kd) values for skeletal muscle microsomes from SHR showed no difference compared with WKY rats irrespective of age. Dihydropyridine binding to heart microsomes, brain microsomes, and solubilized skeletal muscle microsomes exhibited strong calcium dependence. The Ca2(+)-dependent dihydropyridine binding curves for heart showed a Hill slope, and pK 0.5 values for 15-week-old SHR and WKY rats were 0.70 +/- 0.12 and 4.66 +/- 0.12 versus 0.72 +/- 0.12 and 5.66 +/- 0.08 (n = 4, mean +/- SD), respectively, indicating that 15-week-old SHR require 10-fold higher calcium concentration than WKY rats to promote dihydropyridine binding. The pK 0.5 values of calcium for brain and solubilized skeletal muscle calcium channels in 15-week-old SHR were also significantly lower than in WKY rats. This difference first became apparent in SHR and WKY rats as early as 4 and 8 weeks after birth. These results suggest that enhancement of calcium channel density might occur in the heart and brain of SHR in response to elevated blood pressure and that reduced calcium sensitivity of dihydropyridine binding to calcium channels might be a primary characteristic of this rat strain.     

Decreased angiotensin II receptors in subfornical organ of spontaneously hypertensive rats after chronic antihypertensive treatment with enalapril

Angiotensin II (ANG II) receptor density was higher in many brain regions of untreated spontaneously hypertensive rats (SHR) compared to untreated Wistar-Kyoto (WKY) animals. Systemic inhibition of angiotensin converting enzyme with enalapril (25 mg/kg, per os for 14 days) produces a large decrease in ANG II receptors localized exclusively in the subfornical organ (SFO) of the SHR, and no alterations in ANG II receptors in the normotensive WKY rats. Selective decrease of ANG II receptors in the SFO of the genetically hypertensive rats with enalapril may be related to its therapeutic efficacy.     

Angiotensin II binding sites in the superior cervical ganglia of spontaneously hypertensive and Wistar-Kyoto rats after preganglionic denervation

In the superior cervical ganglia (SCG) binding site density of angiotensin II (ANG II) was higher in adult spontaneously hypertensive rats (SHR) (571 +/- 29 fmol/mg protein) compared to that in the adult Wistar-Kyoto rat (WKY) (375 +/- 9 fmol/mg protein, P less than 0.05). The ANG II binding density was significantly decreased in the SCG of SHR (-59%, P less than 0.01) and of WKY (-39%, P less than 0.05) after unilateral preganglionic denervation (operated v sham-operated ganglia). Part of the binding sites in the superior cervical ganglia may be present in or be associated to preganglionic nerves, and the number of these sites is higher in SHR.     

高血压对大鼠血管平滑肌细胞结缔组织生长因子表达水平的影响及其意义

目的:探讨大鼠血管平滑肌细胞(VSMCs)结缔组织生长因子(CTGF)表达水平在高血压血管重构中的变化及其意义。方法:以4周龄及16周龄的自发性高血压大鼠(SHR)为模型,以相同周龄的Wistar-Kyoto(WKY)大鼠为正常对照,采用tail cuff法测量SHR及WKY大鼠尾动脉收缩压。开胸后分离胸主动脉,分别测量胸主动脉中层厚度(M)和管腔内径(L),并计算二者的比值(M/L)。应用免疫荧光技术结合激光共聚焦显微镜观察,对CTGF的表达进行定位及定量检测。采用Western blot分析和实时定量RT-PCR,检测不同周龄的SHR主动脉组织内CT-GF、III型胶原(Col III)蛋白及其mRNA的表达。结果:4周龄SHR主动脉M、L、M/L以及ColⅢ蛋白与mRNA表达水平较同龄的WKY相比,均无显著性差异;但CTGF蛋白及mRNA表达水平均明显增高(P<0.05)。16周龄的SHR与同龄的WKY大鼠相比,胸主动脉的M无明显变化;而L显著增高,M/L显著降低(P<0.01);CTGF和ColⅢ的表达亦显著升高(P<0.01)。结论:实验结果提示,异常的血流动力学因素可调节VSMCs中CTGF的表达,从而引起细胞外基质释放增加,导致血管重构的发生。     

Altered responsiveness of proximal tubule fluid reabsorption of peritubular angiotensin II in spontaneously hypertensive rats

Stimulation of proximal tubular fluid reabsorption by peritubular angiotensin II (Ang II) was examined by split-drop micropuncture in 5- and 12-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY). In WKY, the maximum stimulation occurred at 10(-11) mol/l and the response did not vary with age. In 5-week-old SHR, the dose-response relationship was similar in shape and in the extent of the maximum response but was shifted one half-logarithmic step to the right, indicating decreased sensitivity to Ang II. In contrast, the dose-response relationship was shifted one half-logarithmic step to the left in 12-week-old SHR compared with WKY. Alterations in the responsiveness of the proximal tubule to Ang II in young SHR could contribute to sodium retention observed during development of hypertension in these rats.     

Age-related variations in tissue angiotensin converting enzyme activities: comparison between spontaneously hypertensive and Wistar-Kyoto rats

Angiotensin converting enzyme (ACE) activity was measured by fluorimetry in the plasma, lung, heart, aorta and kidney (cortex and medulla) of 3-, 5-, 8- and 11-week-old spontaneously hypertensive rats (SHR) and compared with that of age-matched Wistar-Kyoto rats (WKY). In the plasma, lung and kidney (cortex and medulla), ACE activity was lower in SHR than in WKY. This was evident as early as the age of 3 weeks. In contrast, there were no differences between SHR and WKY in the aorta and the heart. Age-related variations in ACE activities differed in each tissue and in both groups of rats, but no major modifications were correlated with the development of hypertension. A binding assay was performed with [3H]ramiprilat; affinity (KD) and the maximum number of binding sites (Bmax) were determined in plasma and tissues of 3-week-old SHR and WKY. The KD values were identical in the two groups but Bmax was lower in all SHR tissues except in the heart; these results might be related to the decrease in ACE activity. Our results probably reflect genetic differences in ACE activity between SHR and WKY, and suggest that ACE regulatory mechanisms act differently in each tissue.     

Vascular atrial natriuretic factor receptors in spontaneously hypertensive rats.

OBJECTIVE: The aim was to investigate vascular receptors for atrial natriuretic factor (ANF) in spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Wistar rats (WR) at different ages. METHODS: Relaxation and guanylate cyclase responses of blood vessels to atrial natriuretic factor were investigated, as was the binding of 125I-ANF to vascular membranes and ANF receptor subtypes, using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) in reducing conditions, after solubilisation and irreversible binding of 125I-ANF. RESULTS: Vascular relaxation responses of aorta showed an increased sensitivity to ANF in four week old SHR [pD2 = 8.9 (SEM 0.1) v 8.5(0.1) in WKY rats, p < 0.05] while sensitivity was similar for the three strains at older ages. Production of cyclic GMP in mesenteric arteries in response to 100 nmol.litre-1 ANF was greater (p < 0.05) in SHR than in WKY rats at four weeks of age, but was similar in older rats. The density of binding sites for ANF in mesenteric arteries, however, was lower in SHR at four weeks (p < 0.01), and increased in older rats, becoming similar to that of normotensive rats at 12 weeks of age. Affinity of ANF sites was similar in all strains. The proportion of high and low molecular weight ANF binding peptides in solubilised blood vessel membranes on SDS-PAGE was similar in all strains except in four week old SHR, in which binding to the high molecular weight band (presumably the guanylate cyclase containing receptor) was increased relative to the low molecular weight band (non-cyclase-coupled receptor) in comparison to other strains and ages. CONCLUSIONS: Activity of guanylate cyclase in response to occupancy of ANF receptors may be increased in young SHR. Normal relaxation of blood vessels in response to ANF in older SHR could result in failure to counteract the increased vasoconstrictor activity present in these rats, which could play a role in the increase in blood pressure.     

Neurotransmitter release and vascular reactivity in spontaneously hypertensive rats

This study was designed to investigate neurotransmitter release during the sympathetic nerve stimulation of perfused mesenteric arterial beds of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) at young and adult ages. The role of Ca in neurotransmitter release and vascular responsiveness was also examined by using a Ca-antagonist (verapamil). Pressor responses to electrical nerve stimulation and exogenous noradrenaline were greater in SHR than in WKY. Noradrenaline overflow by electrical nerve stimulation from mesenteric arterial beds was also significantly greater in young SHR than age-matched WKY. However, in adult SHR, the noradrenaline overflow was reduced compared with WKY. After verapamil infusion (5.0 X 10(-7)M approximately 2.5 X 10(-6)M), suppression of the pressor responses and noradrenaline overflow evoked by electrical nerve stimulation was greater in SHR than in WKY at both ages. The pressor responses to exogenous noradrenaline were also inhibited by verapamil more in young SHR than in young WKY. In adult SHR, the inhibition was similar to age-matched WKY. These results suggest that noradrenaline release from sympathetic nerve endings in SHR increase at a young age and decreases in adults, and depends at least partly on Ca-influx at both ages as dose vasoconstrictor reactivity. Therefore, Ca-dependency in SHR at both pre- and post-synaptic sites of neurotransmission may contribute to the pathogenesis of hypertension.     

Enhanced angiotensin converting enzyme binding in arteries from spontaneously hypertensive rats.

AIM: To localize and measure angiotensin converting enzyme (ACE) in different vascular beds of genetically hypertensive rats. METHODS: Quantitative autoradiography using the angiotensin converting enzyme (E.C. 3.4.15.1) inhibitor [125I]351A. RESULTS: [125I]351A binding was significantly increased in the ascending aorta (both adventitia and intima), descending (abdominal) aorta, carotid artery and coronary arteries of adult, 12-week-old spontaneously hypertensive rats (SHR) compared with Wistar-Kyoto (WKY) rats. Increased [125I]351A binding was also present in the descending aorta of 1-week-old SHR compared with age-matched WKY rats, and both groups of young rats had much higher binding than adult rats. No difference in [125I]351A binding was found in the caudal (tail) artery of adult SHR compared with WKY rats. In both the atria and the ventricles of adult SHR, [125I]351A binding was very significantly reduced. CONCLUSIONS: Our results indicate that higher ACE concentrations occur in some arteries of genetically hypertensive rats, and support the hypothesis that local arterial concentrations of ACE affect the development and maintenance of genetic hypertension.     

High angiotensin converting enzyme (kininase II) activity in the cerebrospinal fluid of spontaneously hypertensive adult rats

Angiotensin converting enzyme (ACE, Kininase II, E.C. 3.4.15.1) activity was measured in the cerebrospinal fluid of 4- and 16-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) normotensive controls. Adult SHR showed higher cerebrospinal fluid enzyme activity than normotensive age-matched WKY (19.6 +/- 1 and 32.3 +/- 5 nmol/h per ml in WKY and SHR, respectively, P less than 0.025). Conversely, there were no significant differences in enzyme activity in the cerebrospinal fluid of young animals. Our results support the hypothesis of enhanced activity of the central angiotensin system during the established phase of spontaneous hypertension in rats.     

Cyclic GMP formation of resistance vessel in the development of hypertension in spontaneously hypertensive rats.

We investigated the basal levels and responses of cyclic GMP (cGMP) derived from perfused mesenteric arteries to acetylcholine (ACh) and sodium nitroprusside (SNP) in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) at different ages, in order to evaluate the basal and stimulated release of endothelium-derived relaxing factor (EDRF) from the resistance vessel during the development of hypertension. The mesenteric arteries were removed from 8-, 12- and 20-week-old WKY and SHR, and were perfused with Krebs-Henseleit solution containing 0.2 mM isobutyl methyl xanthine. The effluents from the perfused arteries were corrected before and after infusions of graded doses of ACh or SNP, and the levels of cGMP were measured. The basal levels of cGMP from the mesenteric arteries in the 12- and 20-week-old SHR were significantly lower than those in age-matched WKY. A negative correlation was observed between the basal levels of cGMP and the systolic blood pressure in SHR, but not in WKY, among all ages. On the other hand, there were no differences in the responses of cGMP to infusion of ACh between the WKY and SHR at each age. Moreover, the responsiveness of cGMP to infusion of SNP in the 12-week-old SHR was much higher than that in age-matched WKY. These data suggest that the basal cGMP formation in the arteries which may reflect the basal release of EDRF is reduced in older SHR and is associated with the development of hypertension, and that the stimulated release of EDRF is not associated with the development of hypertension.     

Norepinephrine overflow in perfused mesenteric arteries of spontaneously hypertensive rats

We examined the overflow of endogenous norepinephrine with electrical stimulation, the associated pressor response, and rate of initial neuronal uptake of [3H]norepinephrine in perfused mesenteric arteries of 7- and 13-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The tissues of two rats, a spontaneously hypertensive and a WKY control rat, were simultaneously processed and subjected to the same electrical stimulation. Both absolute and fractional overflow of endogenous norepinephrine during periarterial nerve stimulation (5 and 10 Hz for 1 minute) in the tissue of 7-week-old SHR was significantly greater whereas overflow of 13-week-old SHR was equivalent as compared with that of the age-matched WKY rats. The tissue content of norepinephrine was 20-25% higher in SHR of both ages. There was significantly enhanced [3H]norepinephrine uptake in the tissues of young SHR, but no difference was observed in the older SHR. The pressor response to periarterial nerve stimulation was significantly enhanced in 7-week-old SHR and much more so at the older age as compared with the WKY control rats. Exogenous norepinephrine dose-response curves in the tissues of 7-week-old SHR exhibited a parallel leftward shift, characteristic of a change in sensitivity, whereas that of 13-week-old SHR showed a much steeper slope as compared with the respective WKY control rats. This finding suggests that in addition to smooth muscle supersensitivity, structural alterations had occurred in vasculature of 13-week-old SHR. These data indicate that in SHR both the exocytotic release of norepinephrine and the responsiveness of the vascular smooth muscle cells are enhanced in the developmental stage of hypertension whereas smooth muscle supersensitivity to norepinephrine and nonspecific structural alterations primarily contribute to the maintenance of hypertension at 13 weeks of age.     

Effects of dietary sodium on brain angiotensin II receptors in spontaneously hypertensive rats

The effects of dietary sodium on the characteristics of angiotensin II (A II) receptor sites in the hypothalamus-thalamus-septum-midbrain (HTSM) region were examined in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Twenty-four SHR and 24 WKY were divided into two groups respectively, which were maintained on high sodium diets or low sodium diets for 4 weeks, respectively. The binding capacity and affinity of the A II receptors were measured by radioreceptor assay. In WKY, the binding capacity of the A II receptors in the high sodium group was significantly lower than that in the low sodium group. On the other hand, the binding capacity of A II receptors in the high sodium group was significantly lower than that in the low sodium group. On the other hand, the binding capacity of A II receptors was not significantly different between high and low sodium groups in SHR. The secretion of arginine vasopressin (AVP) increased significantly in SHR with high sodium intake. The present results suggest that in WKY the decrease of the binding capacity of the A II receptors in the HTSM region in response to a high sodium intake serves to attenuate an osmotical stimulus to AVP secretion. However, in SHR such a regulatory mechanism as adjusting the binding capacity of the A II receptors is lacking, and this seems to be responsible, at least in part, for the enhanced secretion of AVP on the sodium loading.