Pulmonary vascular effects of sildenafil on the development of chronic pulmonary hypertension in the ovine fetus.
نویسندگان
چکیده
We investigated the pulmonary vascular effects of prophylactic use of sildenafil, a specific phosphodiesterase-5 inhibitor, in late-gestation fetal lambs with chronic pulmonary hypertension. Fetal lambs were operated on at 129 +/- 1 days gestation (term = 147 days). Ductus arteriosus (DA) was compressed for 8 days to cause chronic pulmonary hypertension. Fetuses were treated with sildenafil (24 mg/day) or saline. Pulmonary vascular responses to increase in shear stress and in fetal PaO2 were studied at, respectively, day 4 and 6. Percent wall thickness of small pulmonary arteries (%WT) and the right ventricle-to-left ventricle plus septum ratio (RVH) were measured after completion of the study. In the control group, DA compression increased PA pressure (48 +/- 5 to 72 +/- 8 mmHg, P < 0.01) and pulmonary vascular resistance (PVR) (0.62 +/- 0.08 to 1.15 +/- 0.11 mmHg x ml(-1) x min(-1), P < 0.05). Similar increase in PAP was observed in the sildenafil group, but PVR did not change significantly (0.54 +/- 0.06 to 0.64 +/- 0.09 mmHg x ml(-1) x min(-1)). Acute DA compression, after brief decompression, elevated PVR 25% in controls and decreased PVR 35% in the sildenafil group. Increased fetal PaO2 did not change PVR in controls but decreased PVR 60% in the sildenafil group. %WT and RVH were not different between groups. Prophylactic sildenafil treatment prevents the rise in pulmonary vascular tone and altered vasoreactivity caused by DA compression in fetal lambs. These results support the hypothesis that elevated PDE5 activity is involved in the consequences of chronic pulmonary hypertension in the perinatal lung.
منابع مشابه
The effect of amlodipine and sildenafil on the NT-proBNP level of patients with COPD-induced pulmonary hypertension.
Pulmonary hypertension (PH) is an important cause of heart failure in chronic obstructive pulmonary disease (COPD). The pro brain natriuretic peptide N-terminal (NT-proBNP) has been suggested as a noninvasive marker to evaluate ventricular function. However, there is no evidence to support the use of NT-proBNP in monitoring the benefits of vasodilators in COPD induced PH. Thus, we used NT-proBN...
متن کاملتعیین شاخص های فارماکوکینتیکی شربت سیلدنافیل در هیپرتانسیون ریوی کودکان
Background and purpose: Pulmonary arterial hypertension (PAH) is a fatal disease affecting patients in all ages that could result in acute and chronic heart failure with high mortality rate. Oral sildenafil is approved to treat PAH in adults and recently in children. There are limited studies on the pharmacokinetics parameters of sildenafil, therefore, this study was designed to determine the p...
متن کاملThe effect of amlodipine and sildenafil on the NT-proBNP level of patients with COPD-induced pulmonary hypertension.
Pulmonary hypertension (PH) is an important cause of heart failure in chronic obstructive pulmonary disease (COPD). The pro brain natriuretic peptide N-terminal (NT-proBNP) has been suggested as a noninvasive marker to evaluate ventricular function. However, there is no evidence to support the use of NT-proBNP in monitoring the benefits of vasodilators in COPD induced PH. Thus, we used NT-proBN...
متن کاملStatins and Pulmonary Hypertension in Chronic Obstructive Lung Disease
Chronic obstructive lung disease (COPD) is a chronic multisystem disease with a considerable burden. One of its most common complications is pulmonary artery hypertension (PAH). It has been demonstrated that the development of PAH is correlated with decreased quality of life and survival. Different medications have been proposed for the treatment of PAH, among which one can name statins. Howeve...
متن کاملProlonged endothelin B receptor blockade causes pulmonary hypertension in the ovine fetus.
Endothelin (ET)-1 contributes to regulation of pulmonary vascular tone and structure in the normal ovine fetus and in models of perinatal pulmonary hypertension. The hemodynamic effects of ET-1 are due to activation of its receptors. The ET(A) receptor mediates vasoconstriction and smooth muscle cell proliferation, whereas the ET(B) receptor mediates vasodilation. In a lamb model of chronic int...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- American journal of physiology. Lung cellular and molecular physiology
دوره 288 6 شماره
صفحات -
تاریخ انتشار 2005