The effects of PNMT inhibitors upon cardiovascular changes induced by hemorrhage in the rat.

Abstract

Rapid bleeding in normotensive Sprague-Dawley rats produces a marked fall in arterial blood pressure and a profound decrease in heart rate. The bradycardia, which is abolished by vagotomy and partially antagonized by atropine, was significantly prolonged by pretreatment with SK&F 64139, a potent in vivo inhibitor of peripheral and central (CNS) phenylethanolamine N-methyltransferase (PNMT). This effect of the drug was accompanied by a prolonged hypotensive period and was not seen with SK&F 29661, a selective inhibitor of peripheral (adrenal) PNMT or with SK&F 72223, a structural analog of SK&F 64139 which has no effect on PNMT. These data suggest that the effects of SK&F 64139 are a result of inhibition of central PNMT and that epinephrine may function as a central neurotransmitter mediating cardiovascular responses to hemorrhage, at least under the conditions of these studies.

• Authors: R G Pendleton, J P McCafferty, J M Roesler
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 66 Issue 1 Pg. 1-10 (Aug 22 1980) ISSN: 0014-2999 [Print] Netherlands
• PMID: 7408955 (Publication Type: Journal Article)

Chemical References

• Catecholamines
• Atropine
• Phenylethanolamine N-Methyltransferase

Topics

• Adrenal Medulla (metabolism)
• Animals
• Atropine (pharmacology)
• Autonomic Nervous System (physiology)
• Blood Pressure (drug effects)
• Brain Stem (metabolism)
• Catecholamines (metabolism)
• Hemodynamics (drug effects)
• Hemorrhage (physiopathology)
• Male
• Phenylethanolamine N-Methyltransferase (antagonists & inhibitors)
• Rats
• Vagotomy