In vitro and in vivo inhibition of renin by fatty acids.
Circulating neutral lipids inhibit the in vitro renin reaction. To identify the inhibitor(s), free fatty acids were added to human renin and homologous substrate. Capric, lauric, palmitoleic, linoleic, and arachidonic acids each inhibited the rate of angiotensin I production in vitro (P less than 0.01). Inhibition by polysaturated fatty acids (linoleic and arachidonic) was less (P less than 0.01) after catalytic hydrogenation of the double bonds. To evaluate an in vivo effect of renin inhibition intra-arterial blood pressure responses to infusions of renin and angiotensin II (5.0 microgram) were measured in anephric rats (n = 6) before and after infusion of linoleic acid (10 mg iv). Mean increase of blood pressure to angiotensin II before (75 mmHg +/- 9) and after (90 +/- 12) linoleic acid did not differ (P greater than 0.05). However, the pressor response to renin after linoleic acid (18 +/- 3) was less (P less than 0.00)) than that before (102 +/- 13). In summary, several fatty acids inhibit the in vitro renin reaction, and in part inhibition is dependent on unsaturation. Linoleic acid also inhibits the in vivo pressor response to renin. These results suggest that fatty acids may modify the measurement of plasma renin activity and may also affect angiotensin production in vivo.
D000803:Angiotensin I / Q000096:biosynthesis; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D007700:Kinetics; D008041:Linoleic Acids / Q000494:pharmacology; D008297:Male; D051381:Rats; D013379:Substrate Specificity; D000092502:Renin Inhibitors
D000803:Angiotensin I; D000804:Angiotensin II; D001095:Arachidonic Acids; D005230:Fatty Acids, Nonesterified; D008041:Linoleic Acids; D000092502:Renin Inhibitors