NITRIC-OXIDE MODULATES SYMPATHETIC CONTROL OF LEFT-VENTRICULAR CONTRACTION IN-VIVO IN THE DOG

Recently, evidence has been presented that nitric oxide (NO) modulates myocardial contraction induced by P-adrenergic stimulation in vitro a nd in vivo. In this study, we investigated whether inhibition of the L -arginine NO system augments the positive inotropic response of the le ft ventricle to direct stimulation of the sympathetic nerves in vivo i n the dog. Electrical stimulation was applied to the left stellate gan glion (LSG) for 1 min at submaximal (5 V, 2.5, 5 and 10 Hz) and supram aximal intensities (10 V, 10 Hz) in twelve anesthetized and vagotomize d dogs. Next, in the same dogs, N-omega-nitro L-arginine methylester ( L-NAME) was infused into the left anterior descending (LAD) coronary a rtery, and LSG stimulation repeated using the same protocol. Finally, L-arginine was infused into the LAD artery, and LSG stimulation repeat ed. We used the maximum of the first derivative of left ventricular pr essure (LV max dP/dt) as an index of the myocardial contractility. pla sma epinephrine and norepinephrine concentrations were measured in the coronary sinus at 5 V, 2.5 Hz before and after L-NAME treatment in fi ve of twelve dogs. L-NAME treatment significantly augmented the inotro pic response of the left ventricle (percent change in the LV max dP/dt ) to LSG submaximal stimulation trains from 164 +/- 13 to .212 +/- 21 (P < 0.03), from 187 +/- 15 to 234 +/- 25 (P < 0.05) and from 220 +/- 19 to 280 +/- 33% (P < 0.05), respectively. This response was reversed by L-arginine treatment. However, the inotropic response to the supra maximal stimulation train did not change after L-NAME and L-arginine t reatment. L-NAME significantly increased plasma norepinephrine concent ration from 0.69 +/- 0.41 to 1.00 +/- 0.52 ng/ml without changing plas ma epinephrine concentration in the coronary sinus. It is concluded th at the inhibition of the L-arginine NO system augmented the positive i notropic effect on the left ventricle during sympathetic nerve stimula tion in normal dogs in vivo. (C) 1998 Elsevier Science B.V. All rights reserved.