Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat.
Increased renal phosphodiesterase-5 activity mediates the blunted natriuretic response to ANP in the pregnant rat.
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肾磷酸二酯酶 5 活性增加介导妊娠大鼠对 ANP 的利尿钠反应减弱。
DOI：
10.1152/ajprenal.00309.2006
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Baylis,Chris
中科院分区：
文献类型：
--
作者：
Knight,Sarah;Snellen,Harold;Humphreys,Michael;Baylis,Chris
Normal rat pregnancy is characterized by plasma volume expansion due to renal sodium retention and is associated with a blunted response to natriuretic stimuli, such as atrial natriuretic peptide (ANP). ANP signals via cGMP, and phosphodiesterases (PDE) inactivate cGMP and terminate the natriuretic response. We previously reported that increased medullary PDE-5 activity occurs in rat pregnancy, which may be the mechanism of the blunted natriuretic effect of ANP. Here, we used anesthetized 16-day pregnant and virgin rats to investigate whether intrarenal infusion of a selective PDE-5 inhibitor, sildenafil, would reverse the blunted response to ANP in pregnancy. We measured blood pressure, renal clearances using inulin andp-aminohippuric acid, and electrolyte excretion at baseline and during an ANP infusion. ANP caused a fall in mean arterial pressure in all groups, and sildenafil induced a further reduction. We observed an increase in sodium excretion with ANP in all rats, but this was blunted in the vehicle-infused pregnant rats. This could not be explained by differences in renal hemodynamics and was of tubular origin, as reflected by the reduced rise in fractional excretion of sodium with ANP in the pregnant rat given vehicle (45 ± 11 vs. 204 ± 49%;P< 0.05). However, intrarenal sildenafil increased the natriuretic response and the rise in fractional excretion of sodium to the virgin value (226 ± 23 vs. 245 ± 73%; not significant), whereas the blunting persisted in the contralateral kidney. This demonstrates that increased intrarenal PDE-5 mediates the blunted natriuretic response to ANP during pregnancy and may contribute to the physiological volume expansion.
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DOI：
10.1126/science.7089575
发表时间：
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期刊：
Science (New York, N.Y.)
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