title: Positive inotropic effect of exogenous and endogenous NO in hypertrophic rat hearts.
abstract: 1. Recent evidence suggests that nitric oxide (NO) modulates the contractile force of isolated cardiomyocytes in a biphasic manner. We sought to examine whether myocardial hypertrophy induced by long-term hypertension changes the effects of NO on myocardial contractility. 2. We used constant flow perfused non-paced Langendorff preparations of hearts of 3 months old Wistar rats (WIS, n = 23) and of stroke-prone spontaneously hypertensive rats (SHR) at the age of 10 months (SHR10, n = 16) and 15 months (SHR15, n = 8). Changes of left ventricular peak pressure (LVP), +dP/dt(max), -dP/dt(max), coronary perfusion pressure (CPP) and heart rate (HR) were recorded after infusion of noradrenaline (NA, 0.1 micromol l(-1)), glyceryl trinitrate (GTN, 1-100 micromol l(-1)), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1-10 micromol l(-1)) and N(omega)-nitro-L-arginine (L-NOARG, 0.1-1 mmol l(-1)). 3. Long-term hypertension induced myocardial hypertrophy and an abnormal response to NA. The relative heart weight (in mg kg(-1)) increased from 2.95 +/- 0.04 (WIS) to 6.67 +/- 0.34 (SHR15), while the increase in +dP/dt(max) induced by NA was absent in SHR15. Hearts of SHR10 showed an intermediate response. 4. Both SNAP and GTN significantly increased LVP, +dP/dt(max) and -dP/dt(max) in hearts of WIS and of SHR. In WIS but not in SHR10, SNAP also increased HR. In SHR10 the lowest concentration of SNAP (1 micromol l(-1)) showed no effect on contractility but a significantly diminished reduction of CPP suggesting inactivation of extracellularly released NO in the coronary circulation of SHR. 5. L-NOARG significantly reduced contractility in hearts of WIS and of SHR to a similar extent. At a concentration of 1 mmol l(-1) L-NOARG also reduced HR. 6. These results suggests that positive inotropic effects of exogenous and endogenous NO are not changed in hypertension induced myocardial hypertrophy.
authors.affiliation: Institut für Pharmakologie, Heinrich-Heine-Universität, Düsseldorf, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Kojda
authors.forename: K
authors.initials: K
authors.lastname: Kottenberg
authors.forename: J P
authors.initials: JP
authors.lastname: Stasch
authors.forename: K
authors.initials: K
authors.lastname: Schrör
authors.forename: E
authors.initials: E
authors.lastname: Noack
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D026423:S-Nitroso-N-Acetylpenicillamine; D013268:Stimulation, Chemical; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D010396:Penicillamine; D009638:Norepinephrine