Nitric oxide does not modulate the hyperpolarization-activated current, I-f, in ventricular myocytes from spontaneously hypertensive rats

Objective: In sinoatrial (SA) node cells, nitric oxide (NO) exerts a dual e ffect on the hyperpolarization-activated current. I-f, i.e. in basal condit ions NO enhances I-f whereas in the presence of P-adrenergic stimulation it decreases it. Recent studies have shown that I-f is present in ventricular myocytes from hypertrophied or failing hearts where it may promote abnorma l automaticity. Since these pathological conditions are associated with inc reased sympathetic tone and upregulation of myocardial NO production. we se t out to investigate whether I-f is similarly modulated by NO in hypertroph ied ventricular myocytes. Methods: Left ventricular myocytes were isolated from 18-20-month-old spontaneously hypertensive rats (SHRs). Membrane curre nt was measured under whole-cell or amphotericin-perforated patch-clamp con ditions, at 35 degreesC. Results: Application of diethylamine-NO (DEA-NO, 1 -100 muM) did not alter the amplitude or voltage dependence of activation o f I-f under basal conditions (half-activation voltage, V-h: control - 82.9/-2.6, DEA-NO - 84.0+/-2.6 mV). Similarly, I-f was not affected by the inhi bition of endogenous NO production (L-NMMA, 500 muM) or guanylate cyclase ( ODQ, 10 muM). Forskolin (10 muM) or isoprenaline (100 nM) elicited a positi ve shift in V-h but subsequent application of DEA-NO did not further affect the properties of I-f. Conclusions: Our results show that, unlike in SA no de cells, in SHR ventricular myocytes basal and adrenergically stimulated I -f is not modulated by exogenous NO or by constitutive NO or cGMP productio n. (C) 2001 Elsevier Science B.V. All rights reserved.