Prolonged sinus node recovery time in humans after the intracoronary administration of a nitric oxide synthase inhibitor

In vitro studies indicate that nitric oxide synthase (NOS) inhibitors alter sinus node automaticity. Moreover, whereas the systemic delivery of N-G-mo nomethyl-L-arginine (L-NMMA), a NOS inhibitor, results in sinus bradycardia and arterial hypertension, its intracoronary administration has little eff ect on sinus heart rate. Therefore whether L-NMMA directly alters sinus nod e function in humans is not known. By using a crossover design, we evaluate d the effect of intracoronary L-NMMA (20 mu mol/min x 10 min) on corrected sinus node recovery time (CSNRT), heart rate, mean arterial blood pressure, electrocardiographic intervals, and coronary artery blood flow in nine men and 13 women aged 48 +/- 12 years. All were in sinus rhythm and had normal baseline CSNRTs. Baseline measurements were made during a dextrose infusio n, and then L-NMMA was administered, and these parameters remeasured. In 11 patients, the infusions were near the origin of the sinus node artery (Con cordant), whereas in the remaining 11, they were into the opposite coronary circulation (Discordant). After L-NMMA, significant prolongations in CSNRT were seen in Concordant (p < 0.001) and Discordant patients (p < 0.05), bu t were most pronounced in the Concordant group (p < 0.05). Although a signi ficant reduction in coronary artery blood flow and nonsignificant changes i n blood pressure and heart rate were observed after L-NMMA, these changes w ere not related to changes in CSNRT (r(2) less than or equal to 0.2; p grea ter than or equal to 0.2). These data support the notion that NO is a modif ier of human sinus node automaticity.