Central noradrenergic activity is responsible for nitroglycerin-induced cardiovascular effects in the nucleus tractus solitarii.
The studies show that unilateral microinjection of nitroglycerin (NTG) into nucleus tractus solitarii (NTS) produce dose-dependent decreases in mean arterial pressure (MAP) and heart rate, but injection of sodium nitroprusside (SNP) into the area induced slight effects. Hypotensive responses to NTG injected into the NTS showed that the compound was 20 times more potent than after i.v. administration. Responses to NTG injected into the NTS were abolished in an additive fashion by either rauwolscine, an alpha 2-adrenoceptor antagonist, or guanethidine which inhibits release of norepinephrine (NE). Injection of prazosin, an alpha 1-adrenoceptor antagonist, into the NTS reduced the hypotensive responses of NTG, but did not alter the bradycardia induced by the drug. Tachycardic responses following i.v. administration of either NTG or SNP were attenuated by bilateral injection of rauwolscine into the NTS, whereas only hypotensive responses to i.v. NTG were reduced by the pretreatment. NTG produced a dose-dependent increase in concentrations of 3,4-dihydroxyphenylalanine in media bathing medulla-pons, which were quantified using high-performance liquid chromatography with electrochemical detection. NE and 3,4-dihydroxyphenylglycol concentrations in media of incubated medulla-pons slices were simultaneously increased following higher concentrations of NTG. The results suggest that NTG in the NTS induces hypotensive and bradycardiac responses, and an increase in turnover of NE may stimulate alpha 2-adrenoceptors and be responsible for the effects of the drug. The NTS may contribute a component of action to the cardiovascular effects of intravenous NTG. The cardiovascular responses of intravenous SNP appear to involve peripheral action.
Ma
S X
SX
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Long
J P
JP
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004295:Dihydroxyphenylalanine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology*; D011149:Pons / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects; D015016:Yohimbine / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D009599:Nitroprusside; D015016:Yohimbine; D008734:Methoxyhydroxyphenylglycol; D004295:Dihydroxyphenylalanine; D005996:Nitroglycerin; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine; D006145:Guanethidine