RELAXIN-INDUCED INCREASED CORONARY FLOW-THROUGH STIMULATION OF NITRIC-OXIDE PRODUCTION

1 Relaxin (RLX) is a multifunctional hormone which, besides its role i n pregnancy and parturition, has also been shown to influence the card iovascular system. In this study, we investigated the effect of RLX on coronary flow of rat and guinea-pig hearts, isolated and perfused in a Langendorff apparatus. RLX was either added to the perfusion fluid a t a concentration of 5 x 10(-9) M for a 20-min perfusion, or given as a bolus into the aortic cannula at concentrations of 10(-9) M, 5 x 10( -9) M and 10(-8) M dissolved in 1 mi of perfusion fluid.2 RLX, given e ither for a 20-min perfusion or as a bolus in the aortic cannula to gu inea-pig and rat isolated hearts, increased the coronary flow and the amount of nitrite, a stable end-product of nitric oxide (NO) metabolis m, that appeared in the perfusates in a concentration-dependent fashio n. 3 The increase in coronary flow and in nitrite in the perfusates in duced by RLX was significantly reduced by pretreatment with the nitric oxide synthase (NOS) inhibitor, N-G-monomethyl-L-arginine (L-NMMA, 10 (-4) M). 4 The effects of RLX on coronary flow and nitrite amounts in the perfusates were compared with those induced by the endothelium-dep endent vasodilator agent, acetylcholine (ACh, 10(-8) - 10(-7) M), and by the endothelium-independent vasodilator agent, sodium nitroprusside (SNP, 10(-7) - 10(-6)M). The results obtained show that RLX is more e ffective than ACh and SNP in increasing coronary flow. 5 The results o f this study show that RLX increases coronary flow through stimulation of NO production; hence this hormone should be regarded as a novel ag ent capable of improving myocardial perfusion.