Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.
OBJECTIVE
We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent.


METHODS
Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily.


RESULTS
Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment period, and these effects were lost when progesterone treatment was stopped. Again, at these doses calcitonin gene-related peptide and progesterone were each ineffective alone.


CONCLUSIONS
Calcitonin gene-related peptide reverses the N(G)-nitro-L-arginine methyl ester-induced hypertension during pregnancy, when progesterone levels are elevated, but not post partum or in ovariectomized nonpregnant rats. The blood pressure-lowering effects of calcitonin gene-related peptide were restored in both postpartum and ovariectomized rats with progesterone treatment. Therefore we conclude that progesterone modulates vasodilator effects of calcitonin gene-related peptide in hypertensive rats.
Gangula
P R
PR
Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston 77555-1062, USA.
Wimalawansa
S J
SJ
Yallampalli
C
C
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000627:therapeutic use*; D004347:Drug Interactions; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D019331:NG-Nitroarginine Methyl Ester; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000139:chemically induced / Q000188:drug therapy; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology*; D011644:Puerperal Disorders / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation; D014664:Vasodilation / Q000187:drug effects*
D011374:Progesterone; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester