We tested the hypothesis that pregnancy might increase diabetes-associated nitric oxide (NO) production and renal hyperfiltration. Two weeks following i.v. streptozotocin (40 mg/kg), mean arterial pressure (MAP) was not modified by diabetes; glomerular filtration rate (GFR), renal plasma flow (RPF) and filtration fraction (FF) were higher in pregnant than in virgin controls and increased by diabetes to a greater extent in pregnant than in virgin rats. Urinary volume (UV), creatinine, albumin and sodium (UNaV) were significantly increased by diabetes. Diabetes led to an increase in renal, cardiac, aortic and uterine but not in placental NO synthase activities. Infusion of NG-nitro-l-arginine (l-NA) caused a dose-dependent reduction in GFR, RPF, plasma NO2-/NO3-, UV and UNaV; in general, diabetes increased these effects to a greater extent in pregnant than in virgin rats. l-NA increased MAP in all groups of rats but did not alter FF. Diabetes did not alter responses of thoracic aorta rings to vasoconstrictor effects of phenylephrine and the vasorelaxant effects of sodium nitroprusside but increased endothelium-dependent relaxant effects of acetylcholine. In general the effects of diabetes of 7 days duration were similar to those described above for diabetes of 14 days duration. These data suggest that diabetes-associated renal hyperfiltration and NO production are augmented by pregnancy.
S Omer, J Shan, DR Varma and S Mulay
P Vaillancourt, S Omer, R Palfree, DR Varma and S Mulay
The main objective of this study was to find out if the reported changes in the aldosterone-suppressant activity of atrial natriuretic peptide (ANP) during different hormonal states in rats are due to a modulation of ANP receptors. In zona glomerulosa cells, ribonuclease protection assay detected mRNAs for guanylate cyclase (GC)-coupled ANP GC-A and GC-B receptors, and for ANP C receptors, which are not coupled to GC. Western analysis using polyclonal anti-GC-A and anti-GC-B receptor antibodies revealed the presence of GC-A but not GC-B receptor proteins in zona glomerulosa cells. Pregnancy (days 7, 16 and 21), oestradiol-17 beta and progesterone decreased mRNAs for all the three ANP receptors in zona glomerulosa cells. Pregnancy decreased GC-A receptor proteins in zona glomerulosa cells, but these recovered to virgin values on day 2 postpartum. ANP receptor mRNAs in zona glomerulosa cells increased by postpartum day 2, but did not reach the values found in virgin rats. Zona fasciculata mainly contained GC-A receptor mRNA. It is concluded that ANP receptors in rat adrenal zona glomerulosa are modulated by pregnancy, oestrogen and progesterone; a decrease in ANP GC-A receptors during pregnancy might explain the accompanying decrease in the aldosterone-suppressant effects of ANP.