Hypertension Produced by a High Sodium Diet in the Borderline Hypertensive Rat (BHR)

The effect of high dietary sodium (8%) on blood pressure in spontaneously hypertensive (SHR), borderline hypertensive (BHR), and normotensive Wistar-Kyoto (WKY) rats was determined weekly by tail cuff plethysmography for one week of baseline and four weeks of diet. After 4 weeks, significant elevations in systolic blood pressure were found in SHR and BHR groups, but not in WKY. BHR studied an additional 4 weeks showed a further progression of hypertension, reaching levels nearly equal to control SHR. Direct measurement of arterial pressure in conscious animals in their home cage confirmed the elevation in pressure in both SHR and BHR groups. Metabolic studies revealed that the high sodium diet reduced body weight in SHR and BHR strains, but not in WKY. Although both urinary volumes and sodium excretion values were significantly lower in SHR and BHR compared with WKY, this effect disappeared when adjustments for body weight were made.

Plasma norepinephrine determinations revealed a significant response to cold stress in all groups. Plasma epinephrine was elevated in all strains in response to cold stress; however, a consistent statistical elevation was seen only in WKY. The BHR is discussed as a model for determining the triggers responsible for environmentally-induced hypertension.     

Castration Lowers and Testosterone Restores Blood Pressure in Several Rat Strains on High Sodium Diets

The objective of this study was to determine the effect of a high sodium diet and prepubertal castration (5-6 weeks) and androgen replacement therapy on blood pressure in male normotensive, borderline hypertensive and hypertensive rats on a high sodium diet between 9-22 weeks of age. The strains used were: Wistar Kyoto-(WKY), spontaneously hypertensive rat-(SHR), and borderline hypertensive rat-(BHR). Castration significantly reduced blood pressure (20-30mmHg) and testosterone replacement in castrated males restored blood pressure in all strains. Plasma norepinephrine (NE) increased with castration in the WKY and SHR strains but decreased in the BHR. However, there was a significant elevation in all strains between the midpoint and endpoint NE values. The high sodium diet did not prevent the blood pressure lowering effect of castration.     

Hypertension Is Not Related to Suppressed Lymphocyte Proliferation but to Elevated NO Synthesis in Vascular Smooth Muscle Cells of Borderline Hypertensive Rat

Hypertensive individuals often exhibit immune abnormalities. We have previously reported that spontaneously hypertensive rats (SHR) had a severely depressed lymphocyte proliferation response caused by excessive nitric oxide (NO) from macrophages and vascular smooth muscle cells (VSMC). However, the development of hypertension was not correlated with the lymphocyte depression and elevated NO synthesis in macrophages. In this study, we investigated the effect of hypertension on lymphocytes and the NO synthesis system in borderline hypertensive rats (BHR). BHR became significantly hypertensive after receiving a high sodium diet. The proliferation response of lymphocytes in hypertensive BHR was similar to that of normotensive BHR fed a normal diet or of Wistar Kyoto rats (WKY). NO production in macrophages of hypertensive BHR was not different from that of normotensive BHR or WKY. However, NO production in VSMC was significantly elevated in hypertensive BHR. A positive correlation between blood pressure and VSMC NO production exists in hypertensive BHR. These results suggested that high blood pressure neither affected the lymphocyte function nor influenced the activation of NO synthesis in macrophages. Hypertension, however, may influence the activation of VSMC NO synthesis. In conclusion, hypertension is not causally associated with immune dysfunction as seen in SHR but is related to enhanced NO synthesis in VSMC.     

有氧运动对自发性高血压大鼠心脏炎症的影响及机制的探讨

目的 探讨有氧运动对自发性高血压大鼠（SHR）心脏炎症的调节及其机制。方法 8周龄雄性SHR大鼠和正常血压对照WKY大鼠各16只,将SHR大鼠随机分为SHR安静组和SHR运动组;将WKY大鼠随机分为WKY安静组和WKY运动组,每组8只。其中运动组大鼠进行8周无负重游泳运动。采用超声心动仪检测心脏功能,用ELISA试剂盒检测心脏炎症因子TNF-α和IL-1β的含量,Western blot法检测心脏叉头框蛋白1（FoxO1）、p65 NF-κB、磷酸化Akt（p-Akt）和总Akt（t-Akt）的表达。结果 与WKY安静组大鼠相比,SHR安静组大鼠左心室p65 NF-κB的表达以及炎症因子TNF-α、IL-1β的含量及FoxO1表达明显升高（P<0.05,P<0.01）,p-Akt的水平下降（P<0.05）;与SHR安静组相比,8周有氧运动能够增强SHR大鼠心脏功能,降低p65 NF-κB的表达以及炎症因子TNF-α和IL-1β的含量（P<0.05）,同时降低FoxO1表达（P<0.05）,提高p-Akt的水平（P<0.05）。8周有氧运动同样能够降低WKY大鼠心脏FoxO1表达（P<0.05）,提高p-Akt的水平（P<0.05）。结论 8周无负重游泳运动能够降低SHR大鼠心脏炎症因子TNF-α和IL-1β的含量,其可能与加强Akt磷酸化水平和下调FoxO1表达有关,确切机制有待进一步研究。     

Stz-Induced Diabetes in Shr and Renovascular Hypertensive Rats: Dissociation Between Changes in Arterial Pressure and Vascular Collagen Synthesis

Streptozotocin (STZ)-induced diabetes depresses the rate of vascular collagen synthesis in the spontaneously hypertensive rat (SHR), but it also reduces arterial pressure (SAP) in this strain. We investigated this phenomenon further by comparing the SHR with the renovascular hypertensive (RVH) rat, because diabetes does not affect SAP in the latter model of hypertension. Renovascular hypertension was induced by clipping the left renal artery of Wistar-Kyoto (WKY) rats; sham-operated WKY were included as normotensive controls. Collagen synthesis of arterial tissue in vitro was quantified as prolyl hydroxylase activity and the rate of radioactive proline incorporation into collagen. Arterial collagen synthesis of nondiabetic SHR and RVH animals was elevated compared to that of the nonhypertensive WKY controls. STZ-induced diabetes (8 weeks) reduced SAP of SHR, but had no effect on SAP of either RVH or normotensive WKY rats. However, diabetes significantly depressed vascular collagen synthesis of both SHR and RVH rats, and, less consistently, of the WKY. The results strongly suggest that STZ-induced diabetes in SHR impairs arterial collagen synthesis independent of associated changes in arterial pressure.     

Exercise-induced myocardial capillary growth in the spontaneously hypertensive rat

Spontaneously hypertensive rats (SHR) were studied to test the hypothesis that endurance exercise training can stimulate capillary growth and offset the decrement associated with the development of myocardial hypertrophy. The exercise group (SHR-T) was trained on a treadmill for 10 weeks at 70-90% maximum VO2 and compared to nontrained SHR and normotensive Wistar-Kyoto (WKY) at 16 weeks of age. Thus, the training program coincided with the development of hypertension and hypertrophy in SHR. Image analysis was used to study capillaries in one micron thick left ventricular tissue samples from perfuse-fixed hearts. Training did not affect left ventricular mass or blood pressure, but reversed the characteristic decrements in capillary surface area (CSA), volume (CV), and numerical density (CD). CSA and CV were most markedly affected by exercise, as mean values for these parameters increased by 31 and 40%, respectively, compared to SHR. The magnitude of these changes approximated the magnitude of hypertrophy as evidenced by left ventricular weight/body weight ratios (42% in SHR and 37% in SHR-T). Anatomical intercapillary distance was also normalized by training (means +/- SEM): SHR-T, 11.65 +/- 0.31; SHR, 13.97 +/- 0.37; WKY, 11.19 +/- 0.37. These data indicate that exercise stimulates capillary growth in the face of developing hypertension and its related left ventricular hypertrophy.     

Central alpha 2-adrenoceptor responsiveness in borderline hypertensive rats.

Increased dietary NaCl intake increases the responsiveness of central nervous system alpha 2-adrenoceptors which regulate the neural control of renal function in spontaneously hypertensive rats (SHR) but not Wistar-Kyoto (WKY) normotensive rats. The borderline hypertensive rat (BHR) is the first filial offspring of the SHR and the WKY. With increased dietary NaCl intake, the BHR develops hypertension and expresses other characteristics of the hypertensive SHR parent. This investigation sought to determine whether increased dietary NaCl intake in the BHR enhances the responsiveness of central nervous system alpha 2-adrenoceptors. Six weeks of increased dietary NaCl intake (8% versus 1% NaCl) in BHR augmented the depressor, bradycardic, renal sympatho-inhibitory and diuretic responses to intracerebroventricular administration of graded doses (5, 25 and 125 micrograms) of the alpha 2-adrenoceptor agonist, guanabenz. The results suggest that the potential for an increased responsiveness of central nervous system alpha 2-adrenoceptors is genetically transmitted to the BHR by the SHR and may be exposed in the BHR by increased dietary NaCl intake.     

Expression of the Na+/H+ exchanger regulatory protein family in genetically hypertensive rats

OBJECTIVE: To examine a possible involvement of a regulatory protein of Na+/H+ exchanger (NHE) in the increased renal NHE activity in spontaneously hypertensive rats (SHR), we investigated mRNA expression of inhibitory members of the NHE regulatory protein family, NHERF1 and NHERF2, in the kidney. DESIGN: Prehypertensive 4-week-old and hypertensive 11-week-old SHR and age-matched Wistar-Kyoto (WKY) rats were used to determine the changes in NHE activity and NHERF family expression in the kidney. Dahl salt sensitive (DS) and resistant rats were also used to examine whether these changes are specific for SHR. METHODS: mRNA expression in the kidney was quantified by RNase protection assay. The NHE activity in primary cultured proximal tubular cells was measured as Na-dependent pHi recovery rate by the NH4Cl prepulse technique with 2'7'-bis-(2-carboxyethyl)-5.6-carboxyfluorescein (BCECF). RESULTS: NHERF1 mRNA expression was significantly decreased in both prehypertensive and hypertensive SHR in comparison with age-matched WKY rats, whereas NHERF2 mRNA expression was significantly increased in SHR only in the hypertensive period. Antihypertensive treatment did not abolish these changes seen in control SHR. On the other hand, hypertensive DS rats fed a high-salt diet showed significant decreases in NHE activity and NHE3 mRNA expression compared with normotensive DS rats fed a low-salt diet, without significant changes in NHERF1 and NHERF2 mRNA expression. CONCLUSION: These results suggest that decreased expression of NHERF1 may be related to the enhanced NHE activity in SHR and that these changes are likely to be genetically determined, whereas the increased NHERF2 expression may be induced as a compensatory mechanism.     

Increase in G(i alpha) protein accompanies progression of post-infarction remodeling in hypertensive cardiomyopathy

Hypertensive cardiac hypertrophy and myocardial infarction (MI) are clinically relevant risk factors for heart failure. There is no specific information addressing signaling alterations in the sequence of hypertrophy and post-MI remodeling. To investigate alterations in beta-adrenergic receptor G-protein signaling in ventricular remodeling with pre-existing hypertrophy, MI was induced by coronary artery ligation in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Ten weeks after the induction of MI, the progression of left ventricular dysfunction and increases in plasma atrial natriuretic peptide (ANP) and cardiac ANP mRNA were more pronounced in SHR than WKY. In addition, the impaired contractile response to beta-adrenergic stimulation was observed in the noninfarcted papillary muscle isolated from SHR. Immunochemical G(s alpha) protein and beta-adrenoceptor density were not significantly altered by MI in both strains. However, immunochemical G(i alpha) was increased (1.5-fold) in the noninfarcted left ventricle of the SHR in which infarction had been induced when compared with that in SHR that underwent sham operation. This increase was observed especially in rats with a high plasma ANP level. Furthermore, there was a positive correlation between G(i alpha) and the extent of post-MI remodeling in WKY. A similar correlation between G(i alpha) and the extent of hypertensive hypertrophy was observed in SHR. In conclusion, the vulnerability of hypertrophied hearts to ischemic damage is greater than that of normotensive hearts. An increase in G(i alpha) could be one mechanism involved in the transition from cardiac hypertrophy to cardiac failure when chronic pressure overload and loss of contractile mass from ischemic heart disease coexist.     

Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+ exchange to Ca2+ removal in rat left ventricular myocytes

Age and hypertension contribute significantly to cardiac morbidity and mortality, however the importance of each during the progression of hypertrophy is unclear. This investigation examined the effect of age and hypertension on Ca(2+) handling in rat ventricular myocytes by comparing a genetic model of hypertension and cardiac hypertrophy (spontaneously hypertensive rat, SHR) with its normotensive control (Wistar-Kyoto rat, WKY) at 5 and 8 months of age. Experiments were performed on single left ventricular myocytes isolated from SHR or WKY hearts. Intracellular Ca(2+) was measured optically using fura-2 or fluo-3. SHR myocytes had a significantly larger cell width and volume and a significantly decreased cell length/width ratio at 5 and 8 months compared to normotensive controls. Age had no effect on cell length, width, volume or the length/width ratio. Ca(2+) transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) content and contraction amplitude were unaffected by age or hypertrophy. However at 8 months the contribution of the SR to Ca(2+) uptake during relaxation decreased, with a concomitant increase in the contribution of Na(+)/Ca(2+) exchanger (NCX) function to relaxation, in SHR and WKY myocytes. The incidence of non-synchronous SR Ca(2+) release decreased with age but not hypertrophy in SHR and WKY myocytes. These results show that the changes in Ca(2+) handling observed during progression of mild hypertrophy in SHR are the same as those that occur during ageing in normotensive control animals and can, therefore, be ascribed to maturation rather than hypertrophy.     

1,2-Diacylglycerol content in myocardium from spontaneously hypertensive rats during the development of hypertension

Summary 1,2-Diacylglycerol (DAG) has been considered to play an important role as an activator of protein kinase C in the signal transduction of inositol phospholipid metabolism. To examine the relation of 1,2-DAG in heart tissues to cardiac hypertrophy associated with hypertension, we measured the amount of 1,2-DAG in spontaneously hypertensive rat (SHR) hearts at 4,10 and 20 weeks of age, and in age-matched normotensive Wistar-Kyoto (WKY) rat hearts using thin-layer chromatography with flame ionization detection (TLC-FID). Significant cardiac hypertrophy was found in 4-week-old SHR, while SHR did not yet have significant hypertension. Major phospholipids such as phosphatidylcholine and phosphatidylethanolamine increased from 4 to 20 weeks in the myocardium, but there was no difference between the two strains. The cholesterol levels of 4- and 20-week-old SHR were significantly higher than WKY rats. The 1,2-DAG contents of SHR hearts were significantly higher than WKY rats at 4 weeks. An increase in the RNA contents of SHR hearts were significantly higher than WKY rats at 4 weeks. An increase in the RNA content was also observed in 4-week-old SHR hearts. However, analysis of the fatty acid composition of 1,2-DAG revealed no difference between the two strains. However, there was no significant difference in the 1,2-DAG content or in its fatty acid composition between SHR and WKY rat hearts at 10 and 20 weeks of age. It is suggested that an increase in the 1,2-DAG content of SHR hearts during the early stages appears related to the initiation of cardiac hypertrophy in SHR hearts before developed hypertension.     

Heat shock protein expression in hearts hypertrophied by genetic and nongenetic hypertension

Summary Genetically hypertensive animals are characterized by greater thermosensitivity and overexpression of heat shock proteins (HSP) upon thermal stimulation. We examined HSP72 expression under conditions of brief coronary occlusion or thermal stimulation, and the effects of the severity of these stimuli and of myocardial hypertrophy on the expression in hearts of spontaneously hypertensive rat (SHR) and Wistar Kyoto rat (WKY) groups, A snare was created around the left coronary artery in the SHR (n=16) and WKY (n=19) groups. In 7 WKY rats, the ascending aorta was banded and a snare was created simultaneously (WKY-AoB). By tying the snare, 4 weeks later, we applied 5- or 10-min coronary occlusion without opening the chest. For thermal stimulation, the SHR (n=13) and WKY (n=11) rats were placed in a 42°C chamber for 15 or 40 min. The mRNA or protein level was estimated 1 or 24h after stimulation. In the SHR vs WKY groups, the mRNA and protein levels were higher after 5-min occlusion or 15-min thermal stimulation. After 10-min occlusion or 40-min thermal stimulation the difference was no longer observed. The overexpression was not observed in the WKY-AoB group despite the presence of hypertrophy similar to that seen in the SHR group (3.11±0.11 vs 3.20±0.06 mg/g in left ventricular weight/body weight). The HSP72 was overexpressed in hearts of genetically hypertensive animals after brief ischemia. Differential expression between the two groups was observed after mild stimuli, but not after more severe stimuli. Cardiac hypertrophy was not a major factor for determining the overexpression of HSP72.     

Blood pressure, electrolyte and adrenal responses in swim-trained hypertensive rats

In order to test the effect of aerobic training on blood pressure, and to examine the putative mechanisms involved, stroke-prone spontaneously hypertensive rats (SHR-SP), borderline hypertensive rats (BHR), and Wistar-Kyoto control rats (WKY) were swim-trained for up to 1.5 h twice-daily for 22 weeks. The BHR were F1 back-cross SHR-SP, WKY. A training effect was observed in the trained rats compared to controls, as demonstrated by slower heart rates, heavier hearts and increased cytochrome oxidase activity in their skeletal muscle. Trained SHR-SP and BHR had significantly lower blood pressures at the end of the intervention period (approximately 10 mmHg) compared to controls. Acute increases in blood pressure with swimming were less in trained than in untrained rats. Trained rats had higher extracellular sodium values than untrained rats. Further, trained SHR-SP and BHR had lower intra-erythrocyte sodium values than controls. Increases in corticosterone, epinephrine and norepinephrine with swimming were less in trained rats than in controls. We conclude that exercise conditioning ameliorates hypertension in rats. The mechanism may involve an effect on cation transmembrane transport, as well as decreased, adrenosympathetic tone. Moreover, these effects may be related.     

Prolonged QT interval is associated with blood pressure rather than left ventricular mass in spontaneously hypertensive rats

QT interval is prolonged in hypertensive individuals, although the factors responsible for this increase are not completely understood. We questioned whether enhanced left ventricular mass (LVM) or increased systemic blood pressure represents the principal factor determining QT prolongation in the period of development of hypertension and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats (SHR). In 12-and 20-week-old SHR (SHR12 and SHR20) and age-matched normotensive Wistar-Kyoto rats (WKY12 and WKY20), arterial systolic blood pressure (sBP) was measured using tail-cuff technique. Orthogonal Frank ECG was registered in anaesthetized animals in vivo, and bipolar ECG was measured in spontaneously beating isolated hearts in vitro. Progressive increase of sBP and LVM resulted in significant QT prolongation in SHR20 as compared to WKY12, WKY20, and also to SHR12 in vivo (WKY12: 82 +/- 9 ms, WKY20: 81 +/- 9 ms, SHR12: 88 +/- 15 and SHR20: 100 +/- 10, respectively; p < 0.05) but not in isolated hearts (WKY20: 196 +/- 39 ms and SHR20: 220 +/- 55, respectively; NS). In whole animals, QT duration was positively related to sBP (r = 0.6842; p < 0.001) but not to LVM (r = 0.1632, NS) in SHR20. The results suggest that QT prolongation in SHR developing hypertension and LVH depends on blood pressure rather than increase in LVM. In this period, myocardial hypertrophy is probably the predisposition for QT prolongation, but the significant change manifests only in the presence of elevated systemic factors.     

Functional and metabolic properties in hearts from aged spontaneously hypertensive rats

The effect of long-term pressure overload on myocardial functional and metabolic alterations was investigated in hearts from spontaneously hypertensive rats of 16 weeks (young SHR) and 44 weeks (aged SHR) and age matched normotensive Wistar Kyoto strain rats (young WKY, aged WKY). The hearts were perfused by working heart mode and whole heart ischemia was induced by one-way valve. Following 20 min of ischemia, the hearts were reperfused for 30 min. The heart-body weight ratio in both SHR groups was significantly higher than in the respective age-matched WKY groups. Coronary flow relative to heart weight in both SHR groups was significantly lower than that of the respective age-matched WKY during both preischemic and reperfused periods. There was no significant difference in the recovery rate of cardiac output between young and aged WKY, whereas the young and aged SHR revealed significantly less recovery than their respective age-matched WKY. Tissue creatine phosphate and energy charge in both aged groups were significantly lower than in the young groups. These results indicate that long-term pressure overload increases susceptibility to ischemia and decreases the myocardial reserve presumably resulting from relative ischemia, whereas deterioration was minimal in the normotensive aged rat heart.     

Sympathetic nerves modify mitochondrial and capillary growth in normotensive and hypertensive rats

We tested the hypothesis that sympathetic nerves influence cardiocyte organelle volumes and capillarity in spontaneously hypertensive rats (SHR) with long-standing hypertension and left ventricular hypertrophy. SHR and their normotensive, Wistar Kyoto (WKY), controls were treated with 6-hydroxydopamine from birth to prevent the establishment of the sympathetic nervous system. To determine whether beta adrenergic receptors were the major pathway of sympathetic influence, another group of SHR and WKY were chronically treated from weaning with the beta 1 adrenergic antagonist, metoprolol. In SHR sympathectomy failed to alter, while metoprolol attenuated, hypertension. Stereological analyses of perfuse-fixed hearts showed that in both SHR and WKY mitochondria/myofibrils volume ratio was increased by long-term sympathectomy, mainly by limiting mitochondrial volume density, even though this intervention failed to alter left ventricular mass. In contrast, long-term beta 1 blockade attenuated hypertrophy in SHR but had no effect on mitochondria/myofibrils volume ratio. Capillary numerical density was increased significantly in sympathectomized SHR and WKY. However, despite this increase, capillary volume density was similar in control and sympathectomized rats, since capillary diameter was less in the latter. Metoprolol-treated SHR showed a trend toward higher capillary numerical densities consistent with their attenuation of hypertrophy. These findings indicate that sympathetic nerves, either directly or indirectly, inhibit cardiocyte mitochondrial growth and capillary proliferation during both normal and pressure-overload induced cardiac enlargement.     

Ontogenic Development of the Elastic Component of the Aortic wall in Spontaneously Hypertensive Rats

In the neonatal stage of development in spontaneously hypertensive rats (SHR), previous studies have shown that arterial pressure is already significantly increased over that of normotensive WKY controls and that other hypertensive characteristics of the cardiovascular system are also in evidence. The present study describes early development of the elastic component of the aortic wall in fetal (days 17,19,21–22 of gestation) and neonatal (days 1,7,14,21 of age) SHR and WKY, to determine whether the early pattern of elastin accumulation differs significantly in hypertensive and normotensive animals. The data indicate that in SHR there is a greater concentration of elastin in the aortic wall, a larger cross-sectional area and an increase in the number of lamellar units, both pre- and postnatally. We conclude that the differences in arterial wall structure which are associated with genetic hypertension are established early in development.     

Myocardial function during chronic food restriction in isolated hypertrophied cardiac muscle

BACKGROUND: The effect of food restriction (FR) on myocardial performance has been studied in normal hearts. Few experiments analyzed the effects of undernutrition on hearts subjected to cardiac overload. The aim of this study was to determine whether chronic FR promotes more significant changes in hypertrophied hearts than in normal hearts. METHODS: Myocardial performance was studied in isolated left ventricular papillary muscle from young male spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar-Kyoto rats (WKY) submitted to FR or to control diet. The animals subjected to FR were fed 50% of the amount of food consumed by control groups for 60 days. Isolated muscles were studied while contracting isometrically and isotonically. RESULTS: FR decreased the body weight and the left ventricular weight in both groups. FR increased the left ventricular weight-to-body weight ratio in the WKY rats and tended to decrease this ratio in SHR (P = 0.055). The arterial systolic pressure was greater in SHR than in WKY groups and did not change with FR. In the animals with normal diet, myocardial performance was better in SHR than in WKY. FR increased time to tension to fall from peak to 50% of peak tension and time to peak tension in the WKY rats and time to peak tension in the SHR. CONCLUSIONS: FR for 60 days has a trend to attenuate the development of cardiac hypertrophy and does not promote more mechanical functional changes in the hypertrophied myocardium than in the normal cardiac muscle.     

Arterial smooth muscle contractions in spontaneously hypertensive rats on a high-calcium diet.

OBJECTIVE: To study the effects of a high-calcium diet upon blood pressure, vascular smooth muscle contractions and intracellular free calcium in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. DESIGN: Eight-week old animals were placed on a normal-calcium diet (1.1% calcium; SHR and WKY rat groups) or a high-calcium diet (2.1% calcium; Ca-SHR and Ca-WKY rat groups) and observed for 12 weeks. METHODS: Blood pressure was measured indirectly by the tail-cuff method and in vitro smooth muscle responses were studied using a standard organ bath chamber. Platelets were used as a cell model for analysis of intracellular free calcium concentration, measured by the fluorescent indicator Quin-2. RESULTS: The blood pressure of Ca-WKY and WKY rats did not differ, but increased systolic blood pressure was attenuated in Ca-SHR compared with SHR. The concentration-response curves of mesenteric arterial rings for potassium chloride and noradrenaline were not affected by the high-calcium diet in either SHR or WKY rats. The time required for total relaxation after washout of contractile agents (washout time) was shortest in WKY and Ca-WKY rats after both agonists, and shorter in Ca-SHR than in SHR after noradrenaline. Smooth muscle responses were also studied by contracting the preparations with noradrenaline and potassium chloride in a calcium-free solution, after which, calcium was added to the organ bath in increasing concentrations. Calcium contraction responses were similar in WKY and Ca-WKY rats; SHR displayed an attenuated response to calcium addition in mesenteric rings stimulated by both agonists. After potassium chloride as agonist, the responses of SHR and Ca-SHR did not deviate but, after noradrenaline, a significant shift in the calcium contraction curve towards the normotensive curve was observed in Ca-SHR. Intracellular free calcium was clearly lower in WKY rats than in SHR, and was significantly reduced by calcium supplementation in the hypertensive but not the normotensive animals. CONCLUSIONS: A reduction in intracellular free calcium concentration and an effect upon receptor-mediated vascular smooth muscle contraction and excitation-contraction coupling may participate in the blood pressure lowering effect of a high-calcium diet.