ROLE FOR THE ENDOGENOUS NATRIURETIC PEPTIDE SYSTEM IN THE CONTROL OF BASAL CORONARY VASCULAR TONE IN DOGS

1. While the natriuretic peptides (atrial, brain and C-type) mediate p otent endothelium-independent vasorelaxing actions in vitro, the role of the endogenous natriuretic peptide system in vascular regulation in vivo remains unclear, 2. HS-142-1 is a novel natriuretic peptide rece ptor antagonist derived from a fungus named Aureobasidium sp, which se lectively blocks particulate guanylate cyclase-linked natriuretic pept ide A and B receptors that bind atrial, brain and C-type natriuretic p eptide, and thus attenuates the generation of cGMP, 3. To characterize the vascular actions of the endogenous natriuretic peptide system in the control of basal coronary and systemic haemodynamics, six normal m ale mongrel anaesthetized dogs Here studied while a second group of fi ve dogs served as a control, HS-142-1 was given as an intravenous bolu s at 3 mg/kg and was studied over five 20 min periods, 4. No significa nt difference after HS-142-1 was observed in mean arterial pressure, h eart rate, cardiac output, right atrial pressure, pulmonary capillary wedge pressure or systemic vascular resistance compared with control, In contrast, a significant increase in coronary vascular resistance an d decrease in coronary blood flow were observed which were different f rom the baseline values and the responses of the control group, 5. The se studies demonstrate that HS-142-1 produces vasoconstriction in the coronary circulation, We conclude that the endogenous natriuretic pept ide system, which is of cardiac and endothelial cell origin, is an imp ortant regulator of basal coronary vascular tone.