Enhanced vascular effects of the Ca(2+) channel agonist Bay K 8644 in pregnant rabbits.
Hemodynamic studies were performed to determine if blunting of vascular pressor responsiveness to vasoconstrictors during pregnancy may be due to impaired L-type voltage-dependent calcium channels (L-VDCC). Bay K 8644 (BAY), an L-VDCC agonist, was infused in pregnant and nonpregnant anesthetized rabbits (10, 20, 40, and 60 microg/kg) and pregnant and nonpregnant conscious, chronically instrumented (conscious) rabbits (10, 25, and 50 microg/kg). BAY infusions resulted in greater elevation of mean arterial pressure in both anesthetized pregnant (n = 6) vs. nonpregnant (n = 6) (P < 0.05) and conscious pregnant (n = 10) vs. nonpregnant (n = 10) rabbits (P < 0.05). Fractional increase over baseline of total peripheral resistance index was greater in pregnant (36 +/- 5 to 78 +/- 14%) vs. nonpregnant rabbits (14 +/- 4 to 52 +/- 6%) (P < 0.02). Cardiac output index did not differ. There was a single high-affinity L-VDCC antagonist aortic binding site with similar number and affinity in pregnant (n = 7) and nonpregnant (n = 7) rabbits. In conclusion, stimulation of L-VDCC induces greater pressor responses in pregnant rabbits with heightened peripheral vasoconstriction. This does not appear to be due to a change in L-VDCC receptor parameters.
Venuto
Rocco
R
Schools of Medicine and Biomedical Science, University at Buffalo, State University of New York, Buffalo, New York 14215, USA. rvenuto@ecmc.edu
Brown
Gail
G
Schoenl
Marion
M
Losonczy
György
G
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000758:Anesthesia; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D003243:Consciousness; D004095:Dihydropyridines / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011817:Rabbits; D013929:Thromboxane B2 / Q000096:biosynthesis; D014316:Tritium
D002120:Calcium Channel Agonists; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D014316:Tritium; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D009543:Nifedipine