Weanling Sprague-Dawley rats were fed on a choline-deficient diet with hydrogenated vegetable oil and corn oil as lipids develop acute renal failure. Pathogenesis of the latter is controversial and an ischemic mechanism has been proposed. Arachidonic acid derivatives are involved in the regulation of vascular tonus. Vasospasm could be due to an increase in tromboxane A2-mediated vasoconstrictio...

Monocyte-endothelial interactions are of fundamental importance in determining the movement of monocytes from the blood stream into the vessel wall. This study reports that two endothelium-derived factors, nitric oxide and prostacyclin, alter in vitro monocyte behavior. Nitric oxide (greater than 10(-5) M) inhibited monocyte adhesion to porcine aortic endothelial cell monolayers, whereas prosta...

Cyclooxygenase (COX)-2 and COX-1 play an important role in prostacyclin production in vessels and participate in maintaining vascular homeostasis. Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, which is crucial in cholesterol biosynthesis. Recently, cholesterol-independent effects of statins have been described. In this study, we evaluated the effect of two...

Prostacyclin (PGI(2)) is a member of the prostaglandin family of bioactive lipids. Its best-characterized role is in the cardiovascular system, where it is released by vascular endothelial cells, serving as a potent vasodilator and inhibitor of platelet aggregation. In recent years, prostacyclin (PGI(2)) has also been shown to promote differentiation and inhibit proliferation in vascular smooth...

Overexpression of adenylyl cyclase (AC) has been proposed as a potential gene therapy strategy to increase cAMP formation in cardiomyocytes and cardiac function in vivo. The impact of AC overexpression on endothelial cells, which will be traversed by genes delivered in vivo, has not been examined. Hence, the goal of the current study was to determine the consequence of AC overexpression on vasc...

Aberrant interactions between heat shock protein (Hsp)90 and its client proteins could contribute to pulmonary hypertension. We tested the hypotheses that 1) the interaction between Hsp90 and its known client protein, endothelial nitric oxide synthase (eNOS), is impaired in pulmonary resistance arteries (PRAs) from piglets with pulmonary hypertension caused by exposure to 3 or 10 days of hypoxi...

Prostacyclin levels are increased in septic patients and several animal models of septic shock, and selective inhibition of cyclooxygenase-2 improved cardiovascular dysfunction in rats treated with lipopolysaccharide (LPS). Here, we examine the specific role of prostacyclin and of the receptor for prostacyclin (IP) in the development of LPS-induced circulatory failure. Intravenous injection of ...

We have previously shown that estrogen treatment increases cerebrovascular cyclooxygenase-1, prostacyclin synthase, and production of prostacyclin. Therefore, vascular tone and prostanoid production were measured to investigate functional consequences of estrogen exposure. Middle cerebral arteries were isolated from ovariectomized female Fischer-344 rats with or without chronic in vivo 17beta-e...

To evaluate the effects of prostacyclin (prostaglandin I2) on pulmonary vascular tone in primary pulmonary hypertension (PPH), we performed right-heart catheterization on seven patients with PPH and made hemodynamic measurements before and after infusing incremental doses of prostacyclin. In maximal doses of 2-12 mg/kg/min (mean 5.7 +/0 3.1 ng/kg/min), prostacyclin reduced mean pulmonary arteri...

To evaluate pulmonary vasoreactivity in children and young adults with primary pulmonary hypertension, we performed cardiac catheterizations on nine patients with primary pulmonary hypertension (nine months to 23 years old) and made hemodynamic measurements: before and after infusing prostacyclin, and before and after administering sublingual nifedipine. Based upon the response to prostacyclin,...