IMPAIRMENT OF CGMP-MEDIATED AND CAMP-MEDIATED VASORELAXATIONS IN RATSWITH CHRONIC HEART-FAILURE

To elucidate pathophysiological alterations in vascular relaxation in rats with chronic heart failure (CHF), guanosine 3',5'-cyclic monophos phate (cGMP)- and adenosine 3',5'-cyclic monophosphate (cAMP)-mediated vasorelaxations in pulmonary artery (PA) and thoracic aorta (TA) of r ats were examined 12 wk after corollary artery ligation. Acetylcholine (Ach)-induced relaxation was attenuated in endothelium-intact segment s of both arteries, whereas sodium nitroprusside-induced relaxation wa s attenuated only in endothelium-intact TA segments of rats with CHF. Vasorelaxations elicited by isoproterenol and NKH-477, a water-soluble forskolin analogue, were diminished mainly in PA segments of the CNF rat. N-G-nitro-L-arginine methyl ester (L-NAME)-induced decrease in cG MP level was less in endothelium-intact TA segments of the rat with CH F (0.20 +/- 0.06 vs. 0.99 +/- 0.26 pmol/mg protein in control), sugges ting that basal nitric oxide (NO) production is reduced in CHF. Treatm ent with L-NAME attenuated the isoproterenol-induced relaxation only i n endothelium-intact TA segments in control rats but not in CE-IF Fats . The results suggest Chat both cGMP- and cAMP-mediated relaxations ar e impaired in CHF, and a I eduction of NO synthesis? presumably in end othelial cells, plays a significant role in pathophysiogical alteratio ns in vessels of rats with CHF.