The responses of baboon cerebral and extracerebral arteries to prostaglandin endoperoxide (PGH2) and prostacyclin (PGI2) were investigated on isolated arteries and in vivo by serial angiography. Both PGH2 and PGI2 could produce dose-dependent contraction or relaxation of isolated arteries. PGH2 induced relaxation was indicative of prostacyclin synthetase activity, the enzyme which converts PGH2...

The structure of the most recently discovered, biologically highly active prostaglandin, PGI2 or prostacyclin, is correctly predicted on biogenetic grounds, and a general synthesis starting with prostaglandins of the F2alpha series is reported. Starting with the biologically active 13,14-dehydro-PGF2alpha, the synthesis involves formation of a 5-bromo-6,9alpha-epoxy derivative, followed by este...

PURPOSE Targeting the prostacyclin pathway is an effective treatment option for pulmonary arterial hypertension (PAH). Patients with PAH have a deficiency of prostacyclin and prostacyclin synthase. Selexipag is an orally available and selective prostacyclin receptor (IP receptor) agonist. Selexipag is hydrolyzed to its active metabolite ACT-333679, also a selective and potent agonist at the IP ...

Effective delivery of continuous renal replacement therapy (CRRT) depends on the longevity of the filter and circuit used in the CRRT machine. Safe and effective anticoagulation is crucial for maintaining the patency of these circuits. In children, heparin and citrate are the commonly used anticoagulants but they are limited by serious side effects and thus calls for meticulous monitoring. In c...

Prostacyclin is an endogenous mediator that shows potent platelet inhibitory activity and powerful relaxation of peripheral resistance vessels. Prostacyclin receptor agonists are valuable drugs in the treatment of various vascular diseases spanning primary pulmonary hypertension to Raynaud's syndrome. Although agonists from various structural classes were synthesized, a common pharmacophore was...

The development of parenteral prostacyclin therapy marked a dramatic breakthrough in the treatment of pulmonary arterial hypertension (PAH). Intravenous (IV) epoprostenol was the first PAH specific therapy and to date, remains the only treatment to demonstrate a mortality benefit. Because of the inherent complexities and risks of treating patients with continuous infusion IV therapy, there is g...

BACKGROUND We tested the hypothesis that bicistronic cyclooxygenase-1 (COX-1)/prostacyclin synthase (PGIS) and COX-1 gene transfer reduce cerebral infarct volume by augmenting synthesis of protective prostaglandins. METHODS AND RESULTS We infused into lateral ventricle of a rat stroke model recombinant adenoviruses (rAd) containing COX-1 (Adv-COX-1), COX-1 and PGIS (Adv-COX-1/PGIS), or Adv-PG...

The slow-reacting substances (SRS) consist of leukotrienes C, D, and E (LTC, -D, -E) 1 and are derived from the lipoxygenase pathway of arachidonic acid (20:4) metabolism. In examining possible mechanisms for the vasoactive effects of SRS (1-4), we found that cultures o f human endothelial cells release the vasodilatory agent, prostacyclin, on exposure to 10 -9 to 10 -6 M LTC (5). Previous repo...

Prostacyclin is an endogenous eicosanoid produced by endothelial cells; through actions on vascular smooth-muscle cells, it promotes vasodilation. Pulmonary arterial hypertension (PAH) is characterized by elevated mean pulmonary artery pressure due to a high pulmonary vascular resistance state. A relative decrease in prostacyclin presence has been associated with PAH; this pathway has thus beco...

We studied whether inhibition of angiotensin converting enzyme stimulates the formation of nitric oxide and prostacyclin in cultured human and bovine endothelial cells by an enhanced accumulation of endothelium-derived bradykinin. Nitric oxide formation was assessed in terms of intracellular cyclic GMP accumulation, prostacyclin release by a specific radioimmunoassay. Inhibition of angiotensin ...