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OBJECTIVE: : In sinoatrial (SA) node cells, nitric oxide (NO) exerts a dual effect on the hyperpolarization-activated current, I(f), i.e. in basal conditions NO enhances I(f) whereas in the presence of beta-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 abnormal automaticity. Since these pathological conditions are associated with increased sympathetic tone and upregulation of myocardial NO production, we set out to investigate whether I(f) is similarly modulated by NO in hypertrophied ventricular myocytes. METHODS: Left ventricular myocytes were isolated from 18-20-month-old spontaneously hypertensive rats (SHRs). Membrane current was measured under whole-cell or amphotericin-perforated patch-clamp conditions, at 35 degrees C. RESULTS: Application of diethylamine-NO (DEA-NO, 1-100 microM) did not alter the amplitude or voltage dependence of activation of 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 inhibition of endogenous NO production (L-NMMA, 500 microM) or guanylate cyclase (ODQ, 10 microM). Forskolin (10 microM) or isoprenaline (100 nM) elicited a positive 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 node cells, in SHR ventricular myocytes basal and adrenergically stimulated I(f) is not modulated by exogenous NO or by constitutive NO or cGMP production.

Type

Journal article

Journal

Cardiovasc Res

Publication Date

07/2001

Volume

51

Pages

51 - 58

Keywords

Adenylyl Cyclases, Adrenergic beta-Agonists, Amphotericin B, Analysis of Variance, Animals, Arrhythmias, Cardiac, Cardiomegaly, Colforsin, Enzyme Inhibitors, Guanylate Cyclase, Hydrazines, Isoproterenol, Male, Membrane Potentials, Nitric Oxide Donors, Nitric Oxide Synthase, Nitrogen Oxides, Oxadiazoles, Patch-Clamp Techniques, Penicillamine, Pyridines, Rats, Rats, Inbred SHR, Sinoatrial Node, omega-N-Methylarginine