Renal amylin binding in normotensive and hypertensive rats: effects of angiotensin converting enzyme inhibition with perindopril.

Abstract

To investigate the effect of angiotensin converting enzyme inhibition with perindopril on the binding density of [125I]-rat amylin in the renal cortex in normotensive Sprague-Dawley rats, renally ablated hypertensive rats and spontaneously hypertensive rats.Sprague-Dawley rats, renally ablated hypertensive rats and spontaneously hypertensive rats were administered either the angiotensin converting enzyme inhibitor perindopril or no treatment.The density of [125I]-rat amylin binding was measured in the renal cortex using autoradiography in vitro. The systolic blood pressure was measured by indirect tail-cuff plethysmography. The plasma renin activity was measured by radioimmunoassay.The density of [125I]-amylin binding was reduced by approximately 50% in Sprague-Dawley and subtotally nephrectomized Sprague-Dawley rats after treatment with perindopril. These changes were associated with a reduction in systolic blood pressure and an increase in plasma renin activity. In contrast, amylin binding in the perindopril-treated spontaneously hypertensive rats was not reduced, despite the prevention of a rise in systolic blood pressure and an increase in plasma renin activity.These findings provide further evidence for the hypothesis that there is an association among renal amylin binding, the renin-angiotensin system and blood pressure for rats of the Sprague-Dawley strain. In contrast, the lack of an effect of angiotensin converting enzyme inhibition on renal amylin binding for rats of the spontaneously hypertensive rat strain is consistent with previous findings that the changes in amylin binding in rats of this strain are not linked directly to the prevailing systemic blood pressure but may be associated with a developmental abnormality in the kidney of these rats.