Chronic NOS inhibition reverses systemic vasodilation and glomerular hyperfiltration in pregnancy.
The chronic role of nitric oxide (NO), independent of prostaglandin synthesis, in the primary peripheral vasodilation, increased glomerular filtration rate (GFR), and renal plasma flow (RPF) in normal pregnancy remains to be defined. The purpose of the present study was to chronically inhibit NOS to return systemic vascular resistance (SVR), cardiac output (CO), GFR, and RPF to nonpregnant values. Pregnant rats received the nitric oxide synthase (NOS) inhibitor, nitro-L-arginine methyl ester (L-NAME), orally from gestational days 7 through 14. Results were compared with nonpregnant and untreated pregnant rats. At 14 days gestation, CO significantly increased in pregnant vs. nonpregnant rats (187 +/- 17 vs. 125 +/- 10 ml/min, P < 0.05) as SVR decreased (0.64 +/- 0.08 vs. 1.08 +/- 0.08 mmHg. ml(-1). min, P < 0.05) and mean arterial pressure was unchanged (117 +/- 5 vs. 125 +/- 2 mmHg, not significant). Pregnant rats also demonstrated increased GFR (3,015 +/- 33 vs. 2,165 +/- 136 microl/min, P < 0.01) and RPF (7,869 +/- 967 vs. 5,507 +/- 290 microl/min, P < 0.05) vs. nonpregnant rats. L-NAME-treated pregnant rats had values for CO (118 +/- 7 ml/min), SVR (1.09 +/- 0.07 mmHg. ml(-1). min), GFR (2,264 +/- 150 microl/min), and RPF (5,777 +/- 498 microl/min), which were no different than nonpregnant animals. In summary, similar to human pregnancy, primary peripheral vasodilation occurs early in rat pregnancy. Furthermore, the hyperdynamic circulation and glomerular hyperfiltration of normal rat midterm pregnancy can be chronically reversed by NOS inhibition. These findings suggest a role for endothelial damage and decreased NO in the pathogenesis of preeclampsia.
Division of Renal Diseases and Hypertension, Department of Medicine, University of Colorado School of Medicine, Denver, Colorado 80262, USA.
M A
MA
Cadnapaphornchai
M
M
Ohara
K G
KG
Morris
M
M
Knotek
B
B
Rogachev
T
T
Ladtkow
E P
EP
Carter
R W
RW
Schrier
D000818:Animals; D004326:Drinking / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000201:enzymology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester