Effect of progesterone-carbachol derivative on perfusion pressure and coronary resistance in isolated rat heart: via activation of the M2 muscarinic receptor.
OBJECTIVE
The present study was designed to investigate the effects of progesterone-carbachol derivative on perfusion pressure and coronary resistance in rats. An additional aim was to identify the molecular mechanisms involved.


METHODS
The Langendorff model was used to measure perfusion pressure and coronary resistance changes in isolated rat heart after progesterone-carbachol derivative alone and after the following compounds; mifepristone (progesterone receptor blocker), yohimbine (α2 adreno-receptor antagonist), ICI 118,551 (selective β2 receptor blocker), atropine (non-selective muscarinic receptor antagonist), methoctramine (antagonist of M2 receptor) and L-NAME (inhibitor of nitric oxide synthase).


RESULTS
The results show that progesterone-carbachol derivative [10(-9) mM] significantly decreased perfusion pressure (P=0.005) and coronary resistance (P=0.006) in isolated rat heart. Additionally, the effect of progesterone-carbachol on perfusion pressure [10(-9) to 10(-4) mM] was only blocked in the presence of methoctramine and L-NAME.


CONCLUSIONS
These data suggest that progesterone derivative exert its effect on perfusion pressure via activation of the M2 muscarinic. In addition, this phenomenon involves stimulation of nitric oxide synthase (NOS).
Laboratory of Pharmaco-Chemistry at the Faculty of Chemical Biological Sciences of the Universidad Autonoma de Campeche, Av. Agustin Melgar s/n, Col Buenavista C.P.24039 Campeche Cam., Mexico.
Lauro
L
Figueroa-Valverde
Francisco
F
Diaz-Cedillo
Elodia
E
Garcia-Cervera
Eduardo Pool
EP
Gomez
Maria
M
Lopez-Ramos
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000031:analogs & derivatives* / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D011374:Progesterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D043585:Receptor, Muscarinic M2 / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects*
C000596150:17-acetyl-10,13-dimethyl-1,2,6,7,8,9,10,11,12,13,14,15,16,17-tetradecahydrocyclopenta(a)phenanthren-3-ylidenecarbamoyloxy)ethyl)trimethylammonium; D043585:Receptor, Muscarinic M2; D011374:Progesterone; D002217:Carbachol