LOW SODIUM-INTAKE CORRECTS ABNORMALITY IN BETA-RECEPTOR MEDIATED ARTERIAL VASODILATION IN PATIENTS WITH HYPERTENSION - CORRELATION WITH BETA-RECEPTOR FUNCTION-INVITRO

被引:61
作者
NASLUND, T [1 ]
SILBERSTEIN, DJ [1 ]
MERRELL, WJ [1 ]
NADEAU, JH [1 ]
WOOD, AJJ [1 ]
机构
[1] VANDERBILT UNIV,MED CTR,SCH MED,DIV CLIN PHARMACOL,NASHVILLE,TN 37232
关键词
D O I
10.1038/clpt.1990.121
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
To determine the contribution of altered β-receptor function in the vasculature to the increased peripheral vascular resistance seen in hypertension, the effects of intra-arterial infusions of isoproterenol and epinephrine on forearm blood flow were determined in 11 male normotensive subjects and 11 male hypertensive subjects during 10 and 250 mmol/day sodium diets. Increased sodium intake from 10 to 250 mmol produced contrasting effects in the hypertensive and normotensive subjects. In the hypertensive subjects, sensitivity to isoproterenol decreased when sodium intake increased (median effective dose increased from 39 [95% confidence limits, 30 to 50] to 70 [95% confidence limits, 42 to 116] ng/min, p < 0.05). On the other hand, in the normotensive subjects increased sodium intake resulted in an increased sensitivity to isoproterenol induced vasodilation (median effective dose decreased from 52 [38 to 71] to 29 [22 to 38] ng/min, p < 0.01). No change occurred in sensitivity to epinephrine or in the maximum vasodilatory response to ischemia during dietary changes. Changes in β-receptors on lymphocyte membranes paralleled the changes seen in vascular sensitivity so that the proportion of receptors exhibiting high affinity for agonists, a reflection of receptor adenylate cyclase coupling, decreased in the hypertensive subjects from 38.0% ± 3.8% when they were receiving 10 mmol/day sodium to 29.6% ± 2.7% when they were receiving 250 mmol/day sodium (p < 0.01). However, the proportion increased from 32.4% ± 3.7% for normotensive subjects receiving 10 mmol/day sodium to 47.1% ± 7.8% for normotensive subjects receiving 250 mmnol/day sodium (p < 0.05). There was a significant correlation between sensitivity to (3-receptor-mediated vasodilation in the vasculature and measures of β-receptor sensitivity on human leukocyte membranes. We conclude that increased sodium intake is associated with increased sensitivity to β-receptor-mediated vasodilation in normotensive subjects but not in hypertensive subjects who appear to lack this facility to compensate for volume expansion. © 1990.
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页码:87 / 95
页数:9
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