DIETARY FATTY-ACID MODULATES GLOMERULAR ATRIAL-NATRIURETIC-PEPTIDE RECEPTOR

Modification of dietary fatty acid (FA) has been shown to affect the incidence of hypertension and coronary artery disease. We studied whether these effects involve changes in the receptor characteristics of vasoactive substance. Characteristics of atrial natriuretic peptide (ANP) receptors were examined in glomeruli isolated from rats fed a diet containing 5% in weight omega-6, 5% omega-3, 20% omega-6, 20% omega-3 polyunsaturated FA or 20% saturated FA (SFA) for > 4 weeks. The FA composition of phospholipids in isolated glomeruli showed an elevation in 20:4 omega-6 (arachidonic acid, AA) in 5% omega-6, 20% omega-6 and 20% SFA, and elevations in 20:5 omega-3 (eicosapentaenoic acid, EPA) in 5% omega-3 and 20% omega-3 groups. The radioligand binding study revealed: (1) in 20% FA group, receptor density (Ro, fmol/mg prot) of ANP was significantly decreased compared to 5% group (262 +/- 13, n = 8 to 120 +/- 13, n = 12) without changes in equilibrium dissociation constant (K(D)), (2) among high FA (20%) groups, type of FA was essential for determining Ro; higher omega-6 was associated with a lower ANP Ro (177 +/- 11 vs. 103 +/- 3 fmol/mg prot, P < 0.05) and K(D) (0.43 +/- .04 vs. 0.27 +/- .02 nM, P < 0.05). To examine whether the alteration in receptor characteristics is mediated by FA, effects of FA were examined in vitro. In cultured mesangial cells, AA, but not EPA, decreased Ro of ANP receptors (48.7 +/- 4.8% of control, P < 0.05) without affecting K(D). AA-induced down-regulation of ANP receptor was not accompanied by changes in ANP-induced cGMP generation. These results from ex vivo and in vitro studies suggest that dietary FA modulates the glomerular C receptor of ANP. The observed effect of FA on glomerular ANP receptor characteristics raises the possibility of the existence of a novel mechanism through which dietary FA intake effects the cardiovascular physiology and pathophysiology through affecting the receptor characteristics of vasoactive substances.