Response of the rat myometrium to phenylephrine in early pregnancy and the effects of 6-hydroxydopamine.
1. The contractile responses of the longitudinal and circular muscle layers of the rat uterus to the alpha 1-adrenoceptor agonist phenylephrine were measured on days 3-6 of gestation. There was a progressive increase in sensitivity to phenylephrine in both muscle layers between days 3 and 6 of gestation. Overall, this amounted to a 13 and 9 fold increase in sensitivity in longitudinal and circular muscles, respectively. In longitudinal muscle the slope of the Hill plot was 2 on day 3 of pregnancy and was decreased to 1 thereafter. 2. The sympathetic nerve terminals innervating the smooth muscle of the uterus were destroyed by administration of 6-hydroxydopamine (2 x 50 mg kg-1) 4-7 days before testing with phenylephrine. Following this treatment there was a significant increase in sensitivity to phenylephrine on day 3 in both muscle layers. After day 4, the longitudinal muscle was less sensitive to phenylephrine. 3. In the longitudinal muscle there was a progressive increase in the contractile response to maximal concentrations of phenylephrine and to high potassium (100 mM) between days 3 and 6 of pregnancy. In the circular muscle the responsiveness to both phenylephrine and potassium remained unchanged between days 3 and 6 of gestation. 6-Hydroxydopamine had no effect on the maximal responses to phenylephrine or high potassium in either muscle layer. 4. In conclusion, denervation supersensitivity of uterine smooth muscle following injection of 6-hydroxydopamine is observed only on day 3 of pregnancy and appears to be replaced by subsensitivity by day 6. The decrease in the slope of the Hill plot in longitudinal muscle after day 3 may be explained by changes in events between activation of alpha 1-adrenoceptors and contraction.
Kaulenas
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A
Department of Physiology, Monash University, Clayton, Victoria, Australia.
Parkington
H C
HC
Coleman
H A
HA
D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D005260:Female; D005865:Gestational Age; D006892:Hydroxydopamines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009121:Muscle Denervation; D009130:Muscle, Smooth / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism; D016627:Oxidopamine; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000294:innervation
D002395:Catecholamines; D006892:Hydroxydopamines; D010656:Phenylephrine; D016627:Oxidopamine; D011188:Potassium