TY - JOUR
T1 - Dietary fatty acid modulates glomerular atrial natriuretic peptide receptor
AU - Awazu, Midori
AU - Yared, Aida
AU - Swift, Larry L.
AU - Hoover, Richard L.
AU - Ichikawa, Iekuni
N1 - Funding Information:
Portions of this study were published in abstract form at the annual meeting of the American Society of Nephrology 1989 (Kidney mt 37:382, 1990) and 1991 (JAm Soc Nephrol 2:393, 1991). These studies were supported by the National Institutes of Health grants DK 37869, DK 26657, 5P30 DK 26657. We thank Teresa Bills, Bradley Harvie, Tracy Moore-Jarrett, Rebecca McPeak, Susan Knobel for their techni- cal assistance, and Mary Beehan in preparing this manuscript.
PY - 1992/8
Y1 - 1992/8
N2 - 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 ω6, 5% ω3, 20% ω6, 20% ω3 polyunsaturated FA or 20% saturated FA (SFA) for >4 weeks. The FA composition of phospholipids in isolated glomeruli showed an elevation in 20:4 ω6 (arachidonic acid, AA) in 5% ω6, 20% ω6 and 20% SFA, and elevations in 20:5 ω3 (eicosapentaenoic acid, EPA) in 5% ω3 and 20% ω3 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 (KD), (2) among high FA (20%) groups, type of FA was essential for determining Ro; higher ω6 was associated with a lower ANP Ro (177 ± 11 vs. 103 ± 3 fmol/mg prot, P < 0.05) and KD (0.43 ± .04 vs. 0.27 ± .02 nM, P < 0.05). To examine whether the alteration in receptor characterisitics 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 KD. 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 affects the cardiovascular physiology and pathophysiology through affecting the receptor characterisitcs of vasoactive substances.
AB - 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 ω6, 5% ω3, 20% ω6, 20% ω3 polyunsaturated FA or 20% saturated FA (SFA) for >4 weeks. The FA composition of phospholipids in isolated glomeruli showed an elevation in 20:4 ω6 (arachidonic acid, AA) in 5% ω6, 20% ω6 and 20% SFA, and elevations in 20:5 ω3 (eicosapentaenoic acid, EPA) in 5% ω3 and 20% ω3 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 (KD), (2) among high FA (20%) groups, type of FA was essential for determining Ro; higher ω6 was associated with a lower ANP Ro (177 ± 11 vs. 103 ± 3 fmol/mg prot, P < 0.05) and KD (0.43 ± .04 vs. 0.27 ± .02 nM, P < 0.05). To examine whether the alteration in receptor characterisitics 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 KD. 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 affects the cardiovascular physiology and pathophysiology through affecting the receptor characterisitcs of vasoactive substances.
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U2 - 10.1038/ki.1992.285
DO - 10.1038/ki.1992.285
M3 - Article
C2 - 1328748
AN - SCOPUS:0026776951
SN - 0085-2538
VL - 42
SP - 265
EP - 271
JO - Kidney International
JF - Kidney International
IS - 2
ER -