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The regulation of both angiotensin receptors and bradykinin receptors during sodium intake is poorly understood. We hypothesized that an altered balance between renal angiotensin type 1 (AT1) receptors and bradykinin type 2 (B2) receptors might contribute to an increase in blood pressure during periods of high-sodium intake. We studied the effects of high-sodium intake on renal AT1 receptors and B2 receptors in 5-6-week-old spontaneously hypertensive rats (SHR) receiving high-sodium chloride (6% NaCl) or mineral salts (10.5%, composition: 57% NaCl, 28% KCl, 12% MgSO4) compared to those receiving a low-sodium (NaCl 0.125%) diet for 10 weeks. Mineral salt intake was included due to its beneficial effects on blood pressure and cardiac hypertrophy. Receptor densities were measured by quantitative autoradiography. AT1 receptors were quantified using incubation with 125I-Sar1-Ile8-angiotensin II and displacement was measured with PD123319 (10 micromol/l), whereas B2 receptors were quantified using 125I-HPP-icatibant and displacement was measured with icatibant (3 micromol/l). Compared to the SHR controls, a further increase in blood pressure occurred after 2 weeks in the 6% NaCl group and after 6 weeks in the mineral salt group. AT1 receptor density increased in the renal cortex by 41% (p

The cardiovascular effects of chronic inhibition of nitric oxide synthesis and dietary salt were studied in 9-wk-old spontaneously hypertensive rats (SHR). N omega-nitro-L-arginine methyl ester (L-NAME, 0.025% in food, about 20 mg/kg/d) was given to rats receiving diets containing low, moderate, and high salt levels (NaCl 0.2%, 1.1%, and 6.0% of the dry weight of the chow) for 3 wk, L-NAME increased systolic blood pressure by 50 to 60 mmHg in all treated groups, as compared with an average rise of 10 to 20 mmHg in the control SHR. The high-salt diet did not further increase blood pressure. L-NAME also induced cardiac and renal hypertrophy, and these changes were aggravated by the high-salt diet. In addition, 19 of the 30 rats treated with L-NAME suffered strokes and all of them had several myocardial infarctions and renal damage, while the rats not treated with L-NAME had no evidence of stroke or myocardial or renal injury. Responses of mesenteric arterial rings in vitro were studied at the end of the experiment. The vascular contractile responses to noradrenaline were increased, and the relaxation responses to acetylcholine were inhibited in the L-NAME treated groups. In addition, the high-salt diet alone tended to inhibit the response to acetylcholine. Plasma renin activity was markedly increased by L-NAME treatment and decreased by the high-salt diet. The 24-h urine protein excretion was increased both by the L-NAME treatment and by the high-salt diet. The combination of L-NAME and the high-salt diet markedly raised the serum creatinine concentration. Our findings show that the coronary and renal functions are particularly vulnerable in SHR during impaired nitric oxide synthesis, and that the end-organ damage is worsened by an increased intake of dietary salt. We suggest that dysfunction of the endothelium is the primary cause of the effects observed in this study.

The present high levels of sodium chloride (regular salt, RS) intake interfere with the therapeutic effects of angiotensin converting enzyme inhibitors. In previous studies a novel potassium-, magnesium- and 1- lysine-enriched and sodium-reduced salt alternative (SA) has been virtually devoid of the hypertensive, left ventricular hypertrophy producing, and life-span shortening effects, characteristic of RS. We therefore compared the influence of SA on the cardiovascular effects of enalapril with that of RS in male stroke-prone spontaneously hypertensive rats (SHRSP). During the 28-day experiment, RS alone produced a marked rise in blood pressure, induced remarkable left ventricular hypertrophy, and caused the death of five out of 18 SHRSP. Oral enalapril treatment did not significantly affect either of the detrimental cardiovascular effects of RS but there were no deaths in the enalapril-treated group. The SA supplemented diet neither caused mortality nor induced any significant rise in blood pressure as compared to control SHRSP, and caused significantly less cardiac hypertrophy than RS. During SA, enalapril had a marked antihypertensive effect and it also completely blocked the salt-induced left ventricular hypertrophy. During SA+enalapril or SA alone, there was no tendency to hyperkalemia in any of the SHRSP. There was not any difference in the plasma renin activity (PRA) between control, RS and SA groups. Enalapril increased PRA to the same extent, approximately three-fold, in the RS and in the SA supplemented SHRSP. Hence, PRA does not explain the marked improvement of the effects of enalapril by SA in comparison to RS. Our findings suggest that replacement of regular salt by the novel salt alternative may remarkably improve the cardiovascular effects of enalapril treatment. (Hypertens Res 1994; 17: 59-69)