Central noradrenergic activity and the cardiovascular effects of nitroglycerin and amyl nitrate.
Intracerebroventricular and i.v. administration of nitroglycerin in anesthetized Sprague-Dawley rats produced dose-dependent decreases in mean arterial pressure and increases in heart rate, but intracisternal injection of the drug induced hypotension and bradycardia. Hypotensive responses to intracisternal injection of nitroglycerin showed that the compound was two to three times more potent than by i.v. administration (six times when comparing the area under the curve). Intravenous sodium nitroprusside produced dose-dependent hypotensive and tachycardiac effects, but minimal responses were induced by i.c.v. and intracisternal injection. Central pretreatment with either yohimbine or rauwolscine antagonized hypotensive responses to i.c.v. and i.v. nitroglycerin, but did not alter the depressor responses induced by i.v. sodium nitroprusside. Tachycardiac responses to i.c.v. nitroglycerin are greater than the responses induced by i.v. administration. Inhalation of amyl nitrite produced marked hypotensive responses, with the dose-response curves being shifted to the right by i.c.v. pretreatment with rauwolscine, but not by i.v. pretreatment. The concentrations of 3,4-dihydroxyphenylglycol and 3-methoxy-4-hydroxyphenylglycol in cerebrospinal fluid were increased by i.v., i.c.v., and intracisternal administration of nitroglycerin, but were not altered by i.v. sodium nitroprusside. The concentrations of dihydroxyphenylacetic acid were elevated by i.v. and i.c.v. injection of nitroglycerin. Results suggest that nitroglycerin stimulates central noradrenergic activity, which may be involved in the component of hypotensive effects of the drug. Reflex tachycardiac responses to nitroglycerin may be further complicated by forebrain stimulation and medulla-mediated bradycardia. Sodium nitroprusside did not demonstrate central activity.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002946:Cisterna Magna / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects*; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid; D009566:Nitrates / Q000008:administration & dosage / Q000494:pharmacology*; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D000439:Pentanols / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology
D009566:Nitrates; D000439:Pentanols; D009599:Nitroprusside; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D005996:Nitroglycerin; C010117:3,4-dihydroxyphenylglycol; C036285:amyl nitrate