Preeclampsia is a pregnancy-specific condition characterized by an imbalance of circulating angiogenic factors and new-onset hypertension. Although current treatment options are limited, recent studies suggest pravastatin may improve angiogenic profile and reduce blood pressure in preeclampsia. We hypothesized pravastatin would restore angiogenic balance and reduce mean arterial pressure (MAP) in rats with reduced utero-placental perfusion pressure (RUPP)-induced hypertension. Pravastatin was administered i.p. (1 mg/kg/day) in RUPP (RUPP+P) and normal pregnant rats (NP+P) from day 14-19 of pregnancy. On day 19, MAP was measured via catheter, conceptus data was recorded and tissues collected. MAP was increased (p<0.05) in RUPP compared to NP dams and pravastatin ameliorated this difference. Pravastatin attenuated decreased fetal weight and plasma VEGF and the RUPP-induced increased sFlt-1 when compared to NP dams. Pravastatin treatment did not improve angiogenic potential in RUPP serum and decreased (P<0.05) endothelial tube formation in NP rats. RUPP rats presented with indices of oxidative stress such as increased placental catalase activity and plasma TBARS along with decreased plasma total antioxidant capacity compared to NP controls and pravastatin attenuated these effects. MAP, fetal weight, plasma VEGF, and plasma sFlt-1 were unchanged in NP+P compared to NP controls. The present data indicate that treatment with pravastatin attenuates oxidative stress and lowers MAP in placental ischemia-induced hypertension, but may have negative effects on circulating angiogenic potential during pregnancy. Further studies are needed to determine if there are long-term deleterious effects on maternal or fetal health following pravastatin treatment during pregnancy-induced hypertension or preeclampsia.

Renal sympathetic denervation (RDNx) has emerged as a novel therapy for hypertension; however, the therapeutic mechanisms remain unclear. Efferent renal sympathetic nerve activity (RSNA) has recently been implicated in trafficking renal inflammatory immune cells and inflammatory chemokine and cytokine release. Several of these inflammatory mediators are known to activate or sensitize afferent nerves. This study aimed to elucidate the roles of efferent and afferent renal nerves in renal inflammation and hypertension in the deoxycorticosterone acetate (DOCA)-salt rat model. Uninephrectomized male Sprague Dawley rats (275–300g) underwent selective afferent-selective RDNx (A-RDNx; n=10), total RDNx (T-RDNx; n=10), or Sham (n=10) and were instrumented for measurement of mean arterial pressure (MAP) and heart rate (HR) by radiotelemetry. Rats received 100mg DOCA (s.c.) and 0.9% saline for 21 days. Resting afferent renal nerve activity (ARNA) in DOCA and Vehicle animals was measured after the treatment protocol. Renal tissue inflammation was assessed by renal cytokine content and T-cell infiltration and activation. Resting ARNA, expressed as a percent of peak afferent nerve activity (%Amax), was substantially increased in DOCA vs. Vehicle (35.8±4.4 vs. 15.3±2.8%Amax). The DOCA-Sham hypertension (132±12 mmHg) was attenuated by ~50% in both T-RDNx (111±8) and A-RDNx (117±5mmHg) groups. Renal inflammation induced by DOCA-salt was attenuated by T-RDNx, and unaffected by A-RDNx. These data suggest ARNA may mediate the hypertensive response to DOCA-salt, but inflammation may be mediated primarily by efferent RSNA. Also, resting ARNA is elevated in DOCA-salt rats, which may highlight a crucial neural mechanism in the development and maintenance of hypertension.

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