Hypotensive and bradycardiac responses to reflex sympathetic inhibition produced by nitroglycerin in rats with sinoaortic deafferentation.
Nitroglycerin (NTG) may cause paradoxical bradycardia and occasional life-threatening hypotension. The mechanism is unclear. In this study, we compared the cardiovascular responses of sodium nitroprusside (SNP) with that of NTG in rats with sinoaortic deafferentation (SAD). Intravenous (i.v.) injection of SNP and NTG produced dose-dependent decreases in mean arterial pressure (MAP). SNP was more effective than NTG in increasing heart rate (HR). After SAD, tachycardiac responses to i.v. SNP were abolished, but i.v. NTG caused bradycardia. SAD enhanced the hypotensive responses of both NTG or SNP after i.v. administration. The bradycardic and hypotensive effects of NTG were attenuated by either bilateral vagotomy or intracisternal (i.c.) pretreatment with 20 nmol rauwolscine, but the responses were not altered by i.v. atropine methylbromide (M-atropine), 0.6 mumol. In contrast, cardiovascular responses to i.v. SNP after SAD were not altered by these pretreatments. Tachycardiac responses to intracerebroventricular (i.c.v.) injection of NTG were reduced by SAD, but SAD did not alter bradycardic responses to i.c. injection of NTG. These results suggest that NTG induces inhibitory reflexes that may contribute to its complex cardiovascular responses in rats. The drug may stimulate peripheral sensory receptors with vagal afferents to the medulla, which then triggers an alpha 2-adrenoceptor-mediated sympathoinhibition.
Ma
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Department of Pharmacology, College of Medicine, University of Iowa, Iowa City 52242.
Long
J P
JP
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D001919:Bradycardia / Q000139:chemically induced; D003714:Denervation; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension / Q000139:chemically induced; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012849:Sinoatrial Node / Q000502:physiology*; D014628:Vagotomy; D015016:Yohimbine / Q000494:pharmacology
D009599:Nitroprusside; D015016:Yohimbine; D001285:Atropine; D005996:Nitroglycerin