Cardiohaemodynamic effects of long-term intravenous administration of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75), a potent coronary vasodilator: comparison with glyceryl trinitrate.
1. Cardiohaemodynamic changes have been studied in beagle dogs treated with intravenous injections of either 300 micrograms/kg of N-(2-hydroxyethyl)nicotinamide nitrate (SG-75) or 30 micrograms/kg of glyceryl trinitrate three times a day for 1-2 months. Throughout the experimental period, no significant changes in general behaviour, body weights and plasma levels of enzymes and substrates were observed in either the SG-75-or glyceryl-trinitrate-treated groups. 2. At 1 and 2 months after the start of chronic drug administrations, the dogs were anaesthetized and measurements were made of resting systemic blood pressure, pulse pressure, heart rate, right atrial pressure, coronary blood flow, aortic blood flow, left ventricular (LV) pressure and LVdP/dt: there were no significant differences between non-treated dogs and dogs treated chronically with SG-75 or glyceryl trinitrate. 3. The effects of the acute intravenous administration of SG-75 and glyceryl trinitrate were examined in dogs pretreated intravenously with SG-75 (300 micrograms/kg) and glyceryl trinitrate (30 micrograms/kg), respectively, three times a day for 1-2 months. The depressor and coronary vasodilator responses to the two drugs remained unchanged in comparison with those in non-treated dogs. 4. These results indicated that, with the doses used, neigher SG-75 nor glyceryl trinitrate produced changes in sensitivity or tolerance after long-term intravenous administration.
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007275:Injections, Intravenous; D008297:Male; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009566:Nitrates / Q000494:pharmacology*; D005996:Nitroglycerin / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
D009566:Nitrates; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D005996:Nitroglycerin