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Role of nitric oxide in the natriuretic and diuretic responses in pregnant rats

Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, Virginia 23501

Submitted 7 June 2003 ; accepted in final form 14 July 2003

Normal pregnancy is characterized by sodium conservation and increase in plasma volume, yet the natriuretic response to acute saline volume expansion (VE) is intact in pregnant rats. Nitric oxide (NO) has been suggested to play a role in renal and cardiovascular adaptations to normal pregnancy. The objective of this study was to determine the role of NO in the natriuretic and diuretic responses to VE during pregnancy. Infusion of N^G-monomethyl-L-arginine (L-NMMA) was used to inhibit NO synthesis. Nine groups of Sprague-Dawley (SD) rats were studied: nonpregnant (NP-VE, n = 7), midterm pregnant (MP-VE, n = 8), and late-term pregnant (LP-VE, n = 7) SD groups that underwent VE alone after a control period; NP-L-NMMA (n = 7), MP-L-NMMA (n = 8), and LP-L-NMMA (n = 7) SD groups that were infused with L-NMMA after a control period; and another three groups of SD rats (NP-VE-L-NMMA, n = 8; MP-VE-L-NMMA, n = 7; and LP-VE-L-NMMA, n = 12) that underwent simultaneous VE and L-NMMA infusion after a control period. The change in fractional excretion of sodium was 7.22 ± 1.03% for NPVE, 9.89 ± 1.85% for NP-L-NMMA, and 17.66 ± 1.85% for NP-VE-L-NMMA (P < 0.05 vs. NP-VE and NP-L-NMMA); 6.61 ± 1.07% for MP-VE, 7.99 ± 1.92% for MP-L-NMMA, and 10.24 ± 1.91% for MP-VE-L-NMMA [not significant (NS) vs. MP-VE and MP-L-NMMA]; 8.20 ± 1.92% for LP-VE, 8.09 ± 0.70% for LP-L-NMMA, and 7.57 ± 1.11% for LP-VE-L-NMMA (both NS vs. LP-VE and LP-L-NMMA). The increase in renal interstitial hydrostatic pressure was significantly greater in all NP compared with pregnant groups with similar experimental intervention (i.e., VE, L-NMMA, or VE-L-NMMA). In conclusion, the natriuretic and diuretic responses to VE and L-NMMA infusion were additive in NP but not in pregnant rats, indicating a possible lower ability of pregnant rats to respond to combined significant natriuretic and diuretic stimuli.

nitric oxide inhibition; renal interstitial hydrostatic pressure; natriuretic response; proximal tubule reabsorption