Vascular receptors for atrial natriuretic peptide in hypertension.
Atrial natriuretic peptide (ANP) is secreted by the heart in response mainly to atrial distension and circulates in plasma in picomolar concentrations. It binds to receptors in blood vessels which it relaxes, renal glomeruli where it induces increased glomerular filtration rate, renal papilla to produce natriuresis, adrenal glomerulosa cells to inhibit aldosterone secretion, and median eminence and pituitary where it may inhibit vasopressin secretion. In experimental models of hypertension plasma levels of ANP are uniformly elevated, except in spontaneously hypertensive rats, in which plasma ANP may only rise transiently. The action of ANP on smooth muscle cells of the blood vessel wall results in production of cyclic GMP, which appears to be the second messenger producing relaxation of pre-contracted blood vessels. Mechanisms other than cGMP generation have been proposed but remain unproven as mediators of ANP action. Receptors for ANP in blood vessels are of two subtypes: B-receptors (or R1-receptors), which contain guanylate cyclase in their structure, and C-receptors (or R2-receptors), which have not been shown to the present to be biologically active. Our studies on vascular ANP receptors are reviewed. In several experimental models of hypertension such as saralasin-insensitive 2-kidney, 1-clip and 1-kidney, 1-clip Goldblatt hypertensive rats and in DOCA-salt hypertensive rats, we have found elevated plasma ANP, as well as decreased binding and ANP-induced vascular relaxation and blood pressure-lowering effects of ANP. Both the B and C ANP receptors appear decreased in density, even after acid washing of membranes to remove any retained circulating ANP.(ABSTRACT TRUNCATED AT 250 WORDS)
Schiffrin
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Experimental Hypertension Laboratory, University of Montreal, Quebec, Canada.
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001808:Blood Vessels / Q000737:chemistry*; D006973:Hypertension / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000032:analysis*
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor