To study vascular actions of synthetic alpha-human atrial natriuretic polypeptide (alpha hANP) in man, forearm blood flow (FBF) was measured by strain-gauge plethysmograph during the continuous infusion of 100 ng/min alpha hANP dissolved in 5% dextrose into the brachial artery in healthy subjects. alpha hANP increased FBF, with the concomitant increase in ipsilateral limb venous plasma concentrations of alpha hANP. Overall, there was a significant linear correlation between the decrements of ipsilateral forearm vascular resistance (FVR) during infusions of alpha hANP and initial FVR levels (r = -0.883, P less than 0.01). Moreover, alpha hANP, at the stepwise increasing doses of 20, 100, and 500 ng/min, increased FBF in a dose-related fashion: alpha hANP elicits a concentration-dependent vasodilation of forearm vascular beds. Concomitantly, infusions of alpha hANP caused a dose-dependent increase in ipsilateral limb venous plasma cyclic guanosine monophosphate (cyclic GMP). Overall, there were direct correlations of FBF either to ipsilateral venous plasma alpha hANP (r = 0.724, P less than 0.01) or to cyclic GMP concentrations (r = 0.637, P less than 0.01). Subsequently, isoosmolar CaCl2 solution was infused into the same brachial artery at a rate of 0.09 meq/min, and then, with a 2.5 +/- 0.2-mg/dl increase in ipsilateral venous serum calcium concentrations the incremental responses of both FBF and plasma cyclic GMP to alpha hANP were severely blunted. There was also a significant positive linear correlation between FBF and venous plasma cyclic GMP during infusions of alpha hANP with the simultaneous administration of CaCl2 (r = 0.807, P less than 0.01). Finally, the addition of CaCl2 infusion did not change the slope of the regression line of the FBF-plasma cyclic GMP relationship during infusions of alpha hANP. Evidence presented suggests that alpha hANP acts directly on the forearm vascular beds in man, eliciting its vascular relaxant effect, possibly by increasing cellular levels of cyclic GMP. Moreover, modest elevations of serum calcium inhibit the alpha hANP-dependent vasodilation, possibly through the suppression of cyclic GMP activation.
T Fujita, Y Ito, H Noda, Y Sato, K Ando, K Kangawa, H Matsuo