Angiotensin II stimulates guanylate cyclase activity in aorta, heart, and kidney

The objective of the present investigation was to determine whether angiotensin II at physiological levels has part of its mechanism of action through stimulation of the activity of guanylate cyclase (EC 4.6.1.2), the enzyme that catalyzes the conversion of guanosine triphosphate to cyclic GMP. Angiotensin II enhanced guanylate cyclase activity three-to fivefold in rat aorta, heart, and kidney at a concentration of 1 nM. Dose-response curves revealed that near maximal stimulation of guanylate cyclase with angiotensin II was observed at a concentration as low as 10 pM. The guanylate cyclase cofactor manganese was necessary for the maximal enhancement of guanylate cyclase by angiotensin II. The data in this investigation suggest that guanylate cyclase may play a role in the mechanism of action of angiotensin II at the cellular level.