Pulmonary hemodynamic response to acute combination and monotherapy with sildenafil and brain natriuretic peptide in rats with monocrotaline-induced pulmonary hypertension.

Background: The lungs of patients with pulmonary arterial hypertension (PAH) exhibit decreased bioavailability of nitric oxide and downstream signaling through cyclic guanosine monophosphate (cGMP). Therapies that enhance cGMP-mediated vasodilation have shown efficacy in treating PAH. We tested the hypothesis that combination therapy with sildenafil, a cGMP phosphodiesterase type 5 inhibitor, and brain natriuretic peptide (BNP), a receptor-mediated guanosine cyclase stimulator, synergistically attenuates monocrotaline-induced PAH in rats compared with either monotherapy.

Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat.

The transgenic (mRen2)27 (Ren2) rat overexpresses mouse renin in extrarenal tissues, causing increased local synthesis of ANG II, oxidative stress, and hypertension. However, little is known about the role of oxidative stress induced by the tissue renin-angiotensin system (RAS) as a contributing factor in pulmonary hypertension (PH). Using male Ren2 rats, we test the hypothesis that lung tissue RAS overexpression and resultant oxidative stress contribute to PH and pulmonary vascular remodeling.