Adrenomedullin attenuates the hypertension in hypertensive pregnant rats induced by N(G)-nitro-L-arginine methyl ester.
We examined the effect of adrenomedullin on the cardiovascular system of an animal model for preeclampsia. An inhibitor of nitric oxide synthase, N(G)-nitro-L-arginine methyl ester (L-NAME), was infused subcutaneously into rats at a constant rate from day 14 of pregnancy to make an animal model for preeclampsia. Adrenomedullin was continuously infused intravenously at a dose of 3 or 10 pmol/h from day 17 of pregnancy. The basal systolic blood pressure was significantly higher in the L-NAME treated rats than in the control rats. The adrenomedullin administration at day 19 of pregnancy showed a significant decrease in the blood pressure in the L-NAME treated rats than in vehicle rats during infusion. The blood pressure of normal pregnant rats did not significantly decrease by adrenomedullin infusion. The adrenomedullin decreased pup mortality of the L-NAME treated rats. Adrenomedullin attenuated the L-NAME induced hypertension and pup mortality. On the other hand, adrenomedullin administration in both pregnant rats in early gestation (5-11 days of pregnancy) and in non-pregnant rats did not show any significant effect on L-NAME-induced hypertension. The adrenomedullin mRNA level was predominantly expressed at high levels in the ovary, uterus and placenta, but at low levels in other tissues in pregnant rats in late gestation. The adrenomedullin mRNA level of the L-NAME treated rats in placenta decreased more than in the normal pregnant rats in late gestation (P < 0.05). These findings suggest that the adrenomedullin might play an important role in the regulation of the cardiovascular system of the mother and fetoplacental unit in rats.
Makino
I
I
Department of Obstetrics and Gynecology, School of Medicine, Fukuoka University, Japan.
Shibata
K
K
Makino
Y
Y
Kangawa
K
K
Kawarabayashi
T
T
D053607:Adrenomedullin; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D015152:Blotting, Northern; D001835:Body Weight / Q000187:drug effects; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005333:Fetus / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000401:mortality; D007262:Infusions, Intravenous; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010455:Peptides / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D011270:Pregnancy, Animal; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D019331:NG-Nitroarginine Methyl Ester