[Sodium nitroprusside and inhibition of coronary vasoconstriction in isolated hearts of guinea pigs].
Recent data suggest that nitrate compounds, beside determining vasodilatation by cGMP-mediated Ca++ uptake in the sarcoplasmic reticulum, may also inhibit vasoconstriction by reducing phosphatidyl inositol bisphosphate hydrolysis, a major step in the biochemical pathway responsible for vasoconstriction induced by a variety of agents including angiotensin II (AII). We assessed the inhibitory effects of Na-nitroprusside (NP) on the coronary resistances induced by increasing doses of AII in Krebs perfused (basal pressure: 2.5-3 KPa) Guinea-pig isolated hearts. AII bolus injections (5 to 100 ng) were given before and 10 min after a 7.6.10(-8) to 7.6.10(-6) M infusion of NP for 10 min. AII produced a highly reproducible, linearly dose-related, increase in perfusion pressure (PP) (5 ng: 4.4 +/- 1.16; 10 ng: 8.1 +/- 2.1; 25 ng: 18.7 +/- 3.06; 50 ng: 23.6 +/- 2.31; 100 ng: 30 +/- 1.37 mmHg) that was persistently and dose-dependently inhibited by NP. Well after (greater than 10 min) full recovery from the initial NP-induced vasodilatation and drop in PP its inhibitory effect was observed, varying from 22.1% at the maximal AII and minimal NP does and 90.6% at the minimal AII and maximal NP doses. This study demonstrates that, apart from causing the well-known immediate vasodilatory response by stimulation of cGMP synthesis, NP also causes delayed inhibition of AII-induced coronary vasoconstriction, possibly by preventing phosphatidyl inositol hydrolysis.
Pizzetti
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Divisione di Cardiologia, Istituto Scientifico H S Raffaele, Milano.
Carandente
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O
Passoni
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Ferrario
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Chierchia
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SL
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism; D006152:Cyclic GMP / Q000096:biosynthesis; D005260:Female; D006168:Guinea Pigs; D006868:Hydrolysis; D066298:In Vitro Techniques; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects*
D010716:Phosphatidylinositols; D000804:Angiotensin II; D009599:Nitroprusside; D006152:Cyclic GMP
Nitroprussiato di sodio ed inibizione della vasocostrizione coronarica in cuori isolati di cavia.