Effects of dihydropyridines on aldosterone secretion in adrenal capsule preparations from pregnant rats.
The primary aim of this study was to determine when sensitivity in the aldosterone response to extracellular potassium (K+) decreases during pregnancy. Second, it tested the hypothesis that calcium channel alterations occur in the adrenal cortex during pregnancy. The decreased sensitivity to K+, observed at 22 days of gestation, was not evident at 15 days and between 18 and 36 h postpartum. Increases in extracellular calcium concentration heightened sensitivity to K+ in adrenal capsule preparations derived from nonpregnant rats but had no effect in pregnant animals. The influence of nifedipine and BAY K 8644 (blocker and activator, respectively, of voltage-operated calcium channels) on the aldosterone response to K+ and to adrenocorticotropic hormone (ACTH) was studied. Sensitivity to K+ in nonpregnant rats decreased in the presence of nifedipine and became similar to that in pregnant rats. Responses to ACTH were not affected by nifedipine. BAY K 8644 produced a larger increase in sensitivity in adrenal capsule preparations from pregnant than from nonpregnant rats, leading to superposition of the two dose-response curves to K+. These results indicate that voltage-operated calcium channels involved in aldosterone secretion are functionally impaired during pregnancy.
Brochu
M
M
Research Center, Sainte-Justine's Hospital, Montréal, Québec, Canada.
Picard
S
S
Jodoin
S
S
St-Louis
J
J
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004095:Dihydropyridines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004095:Dihydropyridines; D000450:Aldosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000324:Adrenocorticotropic Hormone; D011188:Potassium; D002118:Calcium