EXOGENOUS NITRIC-OXIDE REDUCES OXYGEN-CONSUMPTION OF ISOLATED VENTRICULAR MYOCYTES LESS-THAN OTHER FORMS OF GUANYLATE-CYCLASE STIMULATION

We tested the hypothesis that increasing cyclic GMP with nitric oxide (NO) would reduce cardiac myocyte metabolism less than other forms of guanylate cyclase stimulation. The steady state O-2 consumption (VO2) of a suspension of ventricular myocytes in 2.0 mM Ca2+ isolated from h earts of New Zealand white rabbits was measured in a glass chamber usi ng Clark-type oxygen electrode. The cellular cyclic GMP levels, determ ined by radioimmunoassay, were increased by (1) adding 3-morpholinosyd nonimine (SIN-1, 10(-8)-10(-5) M) and nitroprusside (10(-8)-10(-5) M), NO donors-soluble guanylate cyclase stimulators: (2) carbon monoxide (CO, 1.5 x 10(-8)-1.5 x 10(-8) M), soluble guanylate cyclase stimulato r and (3) guanylin (10(-8)-10(-5) M), particulate guanylate cyclase st imulator. The baseline myocyte cyclic GMP level was 86 +/- 13 fmol/10( 5) myocytes with a corresponding VO2 of 268 +/- 21 nl O-2/min per 10(5 ) myocytes. An inverse relationship between cellular cyclic GMP levels and VO2 existed in these myocytes. The regression equations for the f our treatments were: VO2 = -0.45 x [cyclic GMP] + 294.4, r = 0.94 for SIN-1; VO2 = -1.46 x [cyclic GMP] + 444.7, r = 0.96 for CO; VO2 = -1.2 5 x [cyclic GMP] + 389.1, r = 0.84 for guanylin and VO2 = -0.55 x [cyc lic GMP] + 322.8, r = -.79 for nitroprusside. The regression lines of the two NO donors were parallel. A similar result was also evident for the regressions of CO and guanylin. However, the slopes of both the S IN-1 and nitroprusside regression line were significantly less steep t han that of either the CO or guanylin lines. Therefore, VO2 is reduced less for a similar increase in cyclic GMP with NO donors compared to direct stimulation with CO or guanylin. These results suggest that NO has metabolic effects on myocytes in addition to its stimulatory effec ts on cellular cyclic GMP. (C) 1998 Elsevier Science B.V.