X-linked locus associated with hypertensive renal disease susceptibility in Dahl rats

OBJECTIVE: There is increasing evidence that genetic factors contribute to renal disease susceptibility associated with essential hypertension. To what extent these genetic factors act independently of hypertension susceptibility remains undetermined. The present study was undertaken to assess the potential chromosome X influence on target organ renal disease in the Dahl rat model of salt-sensitive hypertension. SUBJECTS AND METHODS: Dahl S, Dahl R, F1(RXS), F1(SXR) and F2(RXS) rat male populations were phenotyped for hypertensive renal disease by measuring the percent of incidence of the Grade IV Raij renal pathology score. Six chromosome X markers informative for our (RXS) intercross were analyzed in our F2 rat population (n = 105) for co-segregation with hypertensive renal disease and blood pressure characterized by radiotelemetry. RESULTS: Comparison of the incidence of renal disease (histologically determined) between F1 reciprocal intercross male progenies reveals a significant chromosome X effect on renal disease [percent incidence of Grade IV Raij renal pathology score in F1 (R female S male) male rats = 2.75 +/- 0.66, and in F1 (S female R male) male rats = 0.67 +/- 0.42; = 0.02]. QTL analysis on an F2(RXS) male population phenotyped for renal disease susceptibility (percent incidence of Grade IV Raij renal pathology score) detects significant linkage to DXRat98 (likelihood ratio statistic = 9.4, P = 0.00223) on chromosome X, corroborating X-linkage of renal disease susceptibility in Dahl rats. CONCLUSIONS: Our results demonstrate the existence of an X-linked locus associated with hypertensive renal disease susceptibility in Dahl rats. Furthermore, the chromosome X markers tested did not co-segregate with hypertension, indicating that the gene(s) on chromosome X influence renal disease susceptibility independent of blood pressure.     

The humoral renal antihypertensive system: nervous and hemodynamic effects in normotensive and unclipped renal hypertensive rats

A series of studies of the humoral renal antihypertensive system in normotensive and 2K 1C-renal antihypertensive rats is outlined. The rapid structural upward resetting of the cardiovascular system in renal hypertensive rats was associated with a structural downward resetting in the vasculature of the hypotensive clipped kidney. Unclipping of this kidney caused a pronounced release of renomedullary depressor agents, explaining the rapid normalization of pressure seen after unclipping. This normalization of pressure masks a state of pronounced functional hypotension in a structurally still hypertensive cardiovascular system, characterized by marked splanchnic vasodilatation and a lack of neurogenic counter-regulation. Only when this state has lasted long enough to normalize the structural upward resettings, characteristic of hypertension does the cardiovascular system return to normal. Further, cross-circulation techniques have shown that the humoral antihypertensive agents suppress tonic sympathetic activity, thereby inhibiting normal reflex counter-regulation of their vasodilator effects. Presumably this occurs via both vagal cardiac afferents and central actions. Further, behavior and awareness become depressed during intense and prolonged renomedullary release. Finally, experiments for which a normotensive kidney is cross-circulated from a normotensive rat suggest that the humoral renomedullary antihypertensive system has its threshold of release set so low as to contribute to normal blood pressure regulation, presumably in reciprocal balance with the renocortical renin-angiotensin system. Stepwise pressure elevations increasingly enhance release of the depressor agents from the cross-perfused kidney.(ABSTRACT TRUNCATED AT 250 WORDS)     

Na,K-ATPase activity in renal tubule cells from Milan hypertensive rats

Several abnormalities of cation transport have been described in the Milan hypertensive rats (MHS). In this study we examined Na,K-ATPase activity in proximal convoluted tubules (PCT) cells and medullary thick ascending limb of Henle cells (TAL) from MHS and from the Milan normotensive rats (MNS). Na,K-ATPase activity was determined as 32P-ATP hydrolysis in single tubule segments. Na,K-ATPase activity (pmol Pi/mm t/h) was significantly higher in MHS than MNS both in PCT (903 +/- 227 n = 8 v 506 +/- 285 n = 12) and TAL (4324 +/- 800 n = 5 v 3063 +/- 625 n = 5). Na,K-ATPase dependent respiration was determined in PCT cell from MNS and MHS. Under basal condition Na,K-ATPase dependent respiration (mumol O2/mg protein/h) was higher in MHS than in MNS (24.2 +/- 1.8 n = 5 v 16.1 +/- 0.4 n = 5). When the cells were Na loaded by amphotericin Na,K-ATPase dependent respiration increased significantly more in MHS than MNS (38.4 +/- 1.6 v 26.8 +/- 2.2 n = 4). Thus, Na,K-ATPase activity is higher in renal tubule cells both at normal intracellular Na and after the cells have been Na loaded. The results indicate that regulation of Na homeostasis in renal tubule cell is different in MHS and MNS.     

Increased susceptibility to hypertensive renal disease in streptozotocin-treated diabetic rats is not modulated by salt intake

Aims/hypothesis  

In early type 1 diabetes mellitus, renal salt handling is dysregulated, so that the glomerular filtration rate becomes inversely proportional to salt intake. The salt paradox occurs in both humans and rats and, with low salt intake, results in diabetic hyperfiltration. We tested whether increased salt intake could reduce the susceptibility to injury of non-clipped kidneys in diabetic rats with pre-existing Goldblatt hypertension.     

Disturbances of renal and erythrocyte calcium handling in rats of the Milan hypertensive strain

Urinary calcium (Ca) excretion and erythrocyte membrane Ca binding and transport were investigated in rats of the Milan hypertensive (MHS) and normotensive strains (MNS). Despite slightly reduced ionized Ca levels in the serum, MHS significantly increased urinary Ca excretion under fasting conditions (P less than 0.01). Urinary Ca was positively related to sodium (Na) excretion in both rat strains; moreover the urinary Ca:Na ratio was significantly enhanced in MHS rats (P less than 0.05). These data suggest that in MHS, Ca reabsorption in the renal tubular cell is reduced independently of disturbances in Na handling. Adenosine triphosphate (ATP)-dependent Ca transport, reflecting the Ca, magnesium (Mg)-ATPase activity (Ca pump), was measured in inside-out vesicles obtained from erythrocyte membranes. This variable was significantly reduced in MHS (P less than 0.01), with no change in the Ca pump affinity constant for Ca. Calcium binding to erythrocyte membranes, measured in the presence of free Ca concentrations comparable with those of the intracellular fluid, was found to be significantly reduced (P less than 0.01) in MHS rats because of the lower number of Ca binding sites. These abnormalities of red blood cell (RBC) Ca handling are in keeping with the increased Ca clearance observed in the kidney. It is not clear whether the disturbances of renal and erythrocyte Ca handling were a genetic primary defect or a secondary change of membrane function.     

高血压家族遗传因素、超重与胰岛素抵抗的关系及其相加作用的研究

为探讨高血压家族遗传因素、超重与胰岛素抵抗（ＩＲ）关系及其相加作用，本研究采用家系调查法，对比分析高血压家系直系亲属正常血压者和对照家系直系亲属的有关参数。两家系均按超重和非超重（ＢＭＩ≥２５ｋｇ／ｍ２或ＢＭＩ＜２５ｋｇ／ｍ２）分组。结果表明：四组间除血糖外，胰岛素及其对数转换值、胰岛素敏感指数均有显著的统计学差异；高血压家系非超重组胰岛素敏感指数显著低于对照家系相应组，调整年龄、性别后，各组间胰岛素水平呈高血压家系超重组＞对照家系超重组＞高血压家系非超重组＞对照家系非超重组，而且，无论高血压或对照家系，超重组胰岛素均显著高于非超重组，高血压家系超重组与其它各组间差异均达到统计学显著性水平。这些结果提示，有家族遗传因素者在高血压发生前就可能存在ＩＲ，且遗传因素和超重对ＩＲ具有相加作用。     

Sodium and glucose transport across renal brush border membranes of Milan hypertensive rats

Sodium transport across luminal membranes of proximal tubules isolated from the kidney cortex of young, prehypertensive rats of the Milan hypertensive strain (MHS) and their corresponding normotensive controls, the Milan normotensive strain (MNS), was measured. A higher sodium uptake was observed in vesicles from MHS, although membrane preparations from both strains behaved similarly as far as enzyme profile and sodium-dependent glucose transport were concerned. In the presence of an inwardly directed sodium gradient, sodium uptake depended on the relative permeability of the counterion: in the presence of 100 mM NaCl, sodium transport in MHS was 26% higher than that in normotensive controls (p less than 0.05). Also, a significantly faster sodium uptake by membrane vesicles from MHS was observed when a pH gradient and an electrical potential difference (inside-negative) were imposed across the membrane. In this condition, sodium uptake by membrane vesicles from MHS was up to 39% higher than that in control MNS (p less than 0.01). Therefore, the difference in sodium transport observed between preparations of luminal membrane from the proximal tubule of MNS and MHS seems to be due to a higher rheogenic sodium pathway in the MHS. The present results are in keeping with previous data showing an increased sodium transport across renal tubules of the MHS and support the hypothesis that the abnormality in sodium and water handling by kidneys from MHS can be related to an alteration in sodium transport across the luminal membrane of the proximal tubule cells.     

Insulin resistance in spontaneously hypertensive rats but not in deoxycorticosterone-salt or renal vascular hypertension.

OBJECTIVE: To investigate whether the reported association between insulin resistance and hypertension in spontaneously hypertensive rats (SHR) is a primary defect or a secondary phenomenon in hypertension. DESIGN: Comparisons of glucose metabolism between three groups of hypertensive rats: deoxycorticosterone (DOCA)-salt hypertensive rats; two-kidney, one clip renovascular hypertensive (RVH) rats; SHR; and their respective control groups. There was also an additional group of weight-matched SHR and respective Wistar-Kyoto (WKY) controls. METHODS: A trace amount of 3H-deoxyglucose (3H-DOG) was administered in vivo to evaluate its plasma half-life and tissue uptake. In vitro adipose tissue segments were incubated with 14C-glucose and increasing doses of insulin. RESULTS: Compared with age-matched WKY rats, SHR had significantly higher insulin levels, longer plasma half-life and lower 3H-DOG uptake by heart and striated muscle. Plasma glucose levels and incorporation of 14C-glucose into CO2, triglycerides and glycogen by adipose tissue in response to increasing insulin concentrations was similar for both groups of SHR and WKY rats. No differences were found between hypertensive rats and controls in either the DOCA or RVH groups. CONCLUSION: Evidence of insulin resistance in spontaneous, but not secondary, rat hypertension indicates that the resistance is a primary rather than a secondary event in hypertension.     

Correlations and otherwise between blood pressure, cardiac mass and resistance vessel characteristics in hypertensive, normotensive and hypertensive/normotensive hybrid rats

We have measured heart weight and properties of 150-200 microns mesenteric resistance vessels from spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), two-kidney, one clip Goldblatt renal hypertensive (RHR) and outbred Wistar rats, as well as in SHR/WKY F2-hybrid rats. All rats were 14-weeks-old. In the SHRs, WKYs, RHRs and Wistars the mean blood pressures (measured intra-arterially) were, respectively: 136, 111, 164 and 100 mmHg. In the SHR/WKYs the systolic blood pressures (measured regularly over a two-week period by the tail cuff method) were normally distributed between the values obtained from control SHRs and WKYs. Relative heart weight and resistance vessel media thickness/lumen diameter ratio correlated (P less than 0.001) with blood pressure between SHRs, WKYs, RHRs and Wistars; however, no significant correlation was seen in SHR/WKYs. By contrast, the calcium sensitivity of the resistance vessel noradrenaline response did correlate (P less than 0.01) with blood pressure in the SHR/WKYs, but did not correlate between the pure strains (calcium sensitivity of the SHR and Wistar vessels was similar, but higher than that of the WKY vessels; induction of renal hypertension did not affect calcium sensitivity). The results suggest that although the cardiac enlargement and increased resistance vessel media/lumen ratio of 14-week SHRs may be advantageous for these animals, these structural abnormalities may not be primary causes of the hypertension. Furthermore, the results indicate that it is the WKYs which are abnormal in having a low calcium sensitivity of their resistance vessels, but suggest also that this reduced sensitivity may be associated with mechanisms which help to keep the WKYs normotensive.     

Insulin resistance adds to endothelial dysfunction in hypertensive patients and in normotensive offspring of subjects with essential hypertension

OBJECTIVES: To evaluate whether endothelium-dependent (nitric oxide-mediated) dilation of the brachial artery (BA) is impaired in patients being treated for essential hypertension (EH), and whether this abnormality can be detected in normotensive offspring of subjects with EH (familial trait, FT); and to investigate the interrelationship between flow-mediated vasodilation (FMD) and hyperinsulinaemia/insulin resistance. DESIGN: Cross-sectional study. SETTING: Angiology department at a teaching hospital. SUBJECTS: The study encompassed 172 subjects, of whom 46 were treated hypertonics aged 40-55 (49) years, and 44 age-matched, normotensive volunteers as controls. We also investigated 41 normotonics with FT aged 20-30 (25) years and 41 age-and sex-matched controls without FT. MAIN OUTCOME MEASURES: Using high-resolution ultrasound, BA diameters at rest, during reactive hyperaemia (endothelium-dependent dilation) and after sublingual glyceryl trinitrate (GTN) application (endothelium-independent dilation) were measured. RESULTS: In hypertonics FMD was significantly lower than in controls [2.4 (2.9) vs. 7.4 (2.5)%; P < 0.00005], as was GTN-induced dilation [12.1 (4.3) vs. 16.1 (4.6)%; P=0.0007]. In subjects with FT, FMD was also decreased compared with the control group [5.8 (4.1) vs. 10.0 (3.0)%; P < 0.00005]. The response to GTN was comparable in both groups of young subjects. FMD was negatively related to insulin concentration in all subjects studied (P < 0.00005). CONCLUSIONS: In treated patients with EH, flow-mediated dilation of the BA as well as endothelium-independent dilation are decreased. In individuals with FT the endothelial function of the peripheral arteries is also altered in the absence of elevated blood pressure. Endothelial dysfunction is related to hyperinsulinaemia/insulin resistance, which could be one of the pathogenetic determinants of EH and its complications.     

The role of haem oxygenase in renal vascular reactivity in normotensive and hypertensive rats

OBJECTIVE: To evaluate the contribution of the haem oxygenase-carbon monoxide (CO) system to renal vascular tone in normotensive Wistar rats and in the stroke-prone spontaneously hypertensive rats (SHR-SPs). METHODS: An isolated perfused rat kidney preparation was used in which perfusion pressure/phenylephrine dose-vasoconstrictor responses were generated. Haemin was given 24 h previously, to induce haem oxygenase-1 (HO-1), and L-NAME (N-omega-nitro-L-arginine methyl ester) was given to block nitric oxide (NO) production. RESULTS: Haemin pretreatment attenuated the phenylephrine-induced rise in perfusion pressure (P < 0.05) but L-NAME had no effect on the magnitude of the renal vasoconstrictor responses to phenylephrine. This suggested that the effect of haemin incubation on renovascular responses did not involve NO production. Pretreatment of the rats with the haem oxygenase inhibitor, tin protoporphyrin IX (SnPP-IX) had no effect on either the basal tone or the phenylephrine-induced contractions in the renal vasculature. By contrast, the renovascular responses to phenylephrine in haemin-treated animals were restored following the coadministration of SnPP-IX. Haemin administration in the SHR-SPs caused a significantly greater reduction in the renovascular responses to phenylephrine compared to those in the normotensive animals (P < 0.05). CONCLUSIONS: Following induction of HO-1, the HO-CO system plays an important role in the regulation of renal responses to an adrenergically induced vasoconstrictor challenge. Moreover, the renal vascular bed of hypertensive animals exhibited a greater propensity to upregulate the HO-CO system, which may provide an important counteractive role against the elevation of blood pressure in hypertension.     

Gender-differences in myocardial adaptation to afterload in normotensive and hypertensive rats

Echocardiographic studies suggest that women appear to exhibit a greater degree of myocardial hypertrophy in response to increased afterload than men. Therefore, gender differences and the role of estrogen and testosterone in the development of myocardial hypertrophy were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Male and female rats were either surgically neutered or underwent a sham operation at 21 days of age. A subgroup of neutered females of each strain received 17beta-estradiol replacement. At 6 months, the heart weight-to-body weight ratio was assessed and correlated with systemic blood pressure. Compared with males, females had significantly smaller body and heart weights in both normotensive and hypertensive strains. Despite this, females consistently had significantly greater heart weight-to-body weight ratios. In females, neutering significantly lowered the heart weight-to-body weight ratio in WKY rats, which was returned to intact levels with estrogen replacement. Female SHR showed similar, but not statistically significant, responses. In males, neutering appeared to result in a higher heart weight-to-body weight ratio in WKY rats, but the opposite was seen in SHR. In addition, there was a significant correlation between arterial blood pressure and heart weight-to-body weight ratio (systolic r=0.45, P=0.0015: diastolic r=0.52, P=0.0002) in intact males and females of both strains, and for a given diastolic pressure, females always exhibited a greater heart weight-to-body weight ratio than males. Thus, a greater degree of myocardial hypertrophy in females appears to be related to the presence of estrogen in both normotensive and hypertensive rats. Females show a stronger relationship between heart/body weight and blood pressure than males, which occurred independent of the presence of estrogen.     

食盐对高血压大鼠及正常血压大鼠心肌纤维化的影响

目的:观察食盐对自发性高血压大鼠(SHR)及正常血压大鼠(WKY)心肌纤维化的影响,并探讨其可能机制。方法:SHR和WKY各20只分别分为两组:①高盐饮食组(SHRSL,n=10和WKYSL,n=10)饮用含2％NaCl溶液;②正常盐饮食组(SHRNS,n=10和WKYNS,n=10)饮用不含NaCl清水,共饲养6周。VG染色和图像处理观察心肌纤维化情况,放免测定心肌局部内皮素-1(ET-1)含量。结果:①SHRSL组心肌间质胶原百分比(CVF)及血管周围胶原面积与血管腔面积百分比(PVCA)显著高于SHRNS(P<0.01),WKYSL组的CVF、PVCA明显高于WKYNs组(P<0.05);②SHRSL组心肌局部ET-1含量显著高于SHRNS组(P<0.01),WKYSL组与WKYNS组心肌局部ET-1含量无差别(P>0.05)。结论:高盐饮食可引起SHR及WKY心肌纤维化,盐负荷后SHR心肌局部ET-1含量的增加可能是SHR心肌纤维化加重的原因之一。     

Microvascular responses to ischemia/reperfusion in normotensive and hypertensive rats

The objective of the present study was to determine whether long-term arterial hypertension renders the microvasculature more vulnerable to the deleterious inflammatory responses elicited by ischemia and reperfusion (I/R). Intravital fluorescence microscopy was used to monitor leukocyte adherence and emigration, platelet-leukocyte aggregation, and albumin extravasation in mesenteric postcapillary venules of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) after 10 minutes of ischemia and subsequent reperfusion. Significant and comparable increases in leukocyte adherence/emigration and the formation of platelet aggregates were elicited by I/R in both WKY and SHR. Albumin extravasation was enhanced after I/R in SHR, but not in WKY. Monoclonal antibodies directed against the adhesion glycoproteins CD18, P-selectin, or ICAM-1 showed similar patterns of protection against the I/R-induced inflammatory responses in WKY and SHR. The enhanced albumin extravasation noted in postischemic venules of SHR was prevented by immunoneutralization of either CD18 on leukocytes or ICAM-1 on endothelial cells. These results suggest that, whereas long-term arterial hypertension does not significantly modify the leukocyte and platelet recruitment normally elicited in venules by I/R, it does result in an exaggerated albumin leakage response, which is mediated by an interaction between beta(2) (CD18) integrins on leukocytes and ICAM-1 on endothelial cells.     

Heterogeneity of endothelium-dependent vasorelaxation in conductance and resistance arteries from Lyon normotensive and hypertensive rats

OBJECTIVES: The nature of endothelial factors in response to acetylcholine (ACh) was investigated in conductance and resistance arteries from Lyon normotensive (LN) and Lyon hypertensive (LH) rats. Differences in endothelial function between the two strains were evaluated. METHODS AND DESIGN: Relaxations to ACh were studied in the aorta and small mesenteric arteries (SMA). The relative contribution of nitric oxide (NO), prostanoids and endothelial-derived hyperpolarizing factor (EDHF) was assessed using appropriate inhibitors. Western blot of endothelial NO synthase was achieved. The membrane potential of smooth muscle cells was assessed using microelectrodes. RESULTS: In LN rats, endothelium-dependent relaxation to ACh involved exclusively NO in the aorta, whereas both NO and EDHF were implicated in SMA. In the latter, relaxation was almost entirely prevented by blockade of either the NO or EDHF pathway, although ACh was still able to produce hyperpolarization in the presence of NO synthase and cyclooxygenase inhibitors. In LH rats, relaxation to ACh was unchanged in SMA but moderately depressed in the aorta, despite unchanged endothelial NO synthase protein expression and sensitivity to NO. In addition, indomethacin, but not a selective cyclooxygenase-2 inhibitor, significantly reduced ACh relaxations in the aorta from LH rats but not from LN rats. CONCLUSIONS: These results document differential endothelial function in a conductance and in resistance arteries from LN rats and LH rats. They show that simultaneous participation of NO and EDHF is required to promote relaxation in SMA from both strains, whereas NO alone accounts for relaxation in aorta from LN rats. In LH rats, aortic relaxation induced by ACh is slightly decreased despite the involvement of vasodilator products from cyclooxygenase-1.     

Fetal liver cell transplantation fails to transfer hypertension from genetically hypertensive rats to normotensive rats of the Lyon strain.

The involvement of an auto-immune mechanism has been suggested in the development and/or the maintenance of hypertension in male, genetically hypertensive rats of the Lyon strain (LH). The aim of this study was to determine whether hypertension may be transferred, by lymphoid cells, from hypertensive donors to male, normotensive rats of the Lyon strain (LN). Experiments designed to induce a resistance to hypertension in LH rats by transfer of lymphoid cells from LN animals were also performed. Since LH and LN are mismatched at the major histocompatibility complex, transfers of fetal liver cells (FLC) from fetuses of 13-14 days gestation were performed. These experiments demonstrate the ability of FLC to allow a prolonged survival (over 17 weeks) without graft versus host disease in the rat. As regards the blood pressure level, no LN recipient having received FLC from LH donor became hypertensive, thus showing that hypertension cannot be transferred by lymphoid cells in normotensive animals. Resistance to hypertension was so weakly transferred to hypertensive rats (results being significantly different only at 10 weeks post-grafting) that it may be considered doubtful.     

Erythrocyte adducin differential properties in the normotensive and hypertensive rats of the Milan strain. Characterization of spleen adducin m-RNA

Previous studies have shown that erythrocytes from the Milan hypertensive strain of rats (MHS) differ from erythrocytes from the control normotensive strain (MNS). These differences are determined within the stem cells, are genetically associated with the development of hypertension, and are similar to those found between the tubular cells of the two strains. Moreover they seem to be dependent upon the presence of the membrane skeleton proteins. In this paper we describe our studies aimed at identifying some precise protein difference between the membrane skeletons of the two strains, which may cause the cellular differences described above. Milan hypertensive strain and MNS rats were immunized with ghost or membrane skeleton extracts prepared from the other or their own strains. Only MHS rats immunized with MNS ghost or membrane skeleton extracts produced an antibody against a 105 KD protein in about 95% of the animals. This protein has been identified with the recently described cytoskeletal protein adducin on the following bases: the protein binds calmodulin (CaM) and protein kinase C (PKc) in a Ca2+ dependent way. It also binds phosphatidylserine, is the substrate of exogenous PKc, and finally it is purified by high salt extraction of Triton-X100 insoluble erythrocyte cytoskeletons followed by affinity chromatography on CaM-sepharose. Using this antibody the isolation from a mouse spleen library, the characterization and sequencing of a partial cDNA clone coding for this protein has been carried out. In conclusion adducin may be considered a very useful tool to test the hypothesis that the cellular differences between MHS and MNS may be caused by a difference in a membrane skeleton protein.     

Calcitonin gene-related peptide in normotensive and spontaneously hypertensive rats

Using specific radioimmunoassay, radioimmunoreceptor analysis and gel filtration, we found that calcitonin gene-related peptides (CGRP) were distributed in various tissues of normotensive rat (WKY) and spontaneously hypertensive rat (SHR), the highest content was in the lumbar spinal cord (1197 +/- 94.8 pg/mg tissue), the lowest in the auricle (15.0 +/- 2.1 pg/mg tissue). Compared with WKY, the plasma CGRP concentration decreased and the CGRP content in abdominal aorta and hypothalamus increased in SHR. By gel filtration, it showed that only one major molecular form of CGRP was present in the tissues. The CGRP specific binding sites were present both in SHR and WKY hearts, but the number of CGRP binding sites in SHR heart was higher and the binding affinity lower than those in WKY heart. Besides, CGRP can reduce the mean arterial pressure (MAP) in the SHR in a dose-dependent way. The above data indicated that CGRP may play an important role in the pathogenesis of hypertension and exert possibly a therapeutic effect on hypertension.     

Cardiac reflexes in normotensive and spontaneously hypertensive rats.

Characteristics of left atrial receptors were studied in normotensive control (Wistar) and spontenaously hypertensive rats. The left atrial pressure was chronically elevated in spontaneously hypertensive rats and at the end of the expiratory phase was 10.3 mm Hg as compared with 4.6 mm Hg in normotensive control rats. The thresholds of the receptor endings were twice as high in the hypertensive as in the normotensive rats (10.2 and 4.6 mm Hg, respectively). In other experiments the reflex inhibition of renal sympathetic outflow was studied during plasma infusion in baroreceptor denervated normotensive and hypertensive rats was was inhibited at a lower left atrial pressure in the former. These differences are attirubted to decreased distensibility of the left atrium in spotaneously hypertensive rats. The reflex splanchnic nerve inhibition with volume load also was recorded in awake rats. At a 10 percent increase in blood volume, splanchnic outflow was more significantly decreased in spotaneously hypertensive than in normotensive rats. The mechanism underlying such a hyperreactive volume receptor response is unknown, but a less distensible venous system, centrally or peripherally, might be a contributing factor.