Vascular resistance prostaglandins

Mecfianism of Action A prostaglandin that dilates systemic and pulmonary arterial vascular beds, alters pulmonary vascular resistance, and suppresses vascular smooth muscle proliferation. Therapeutic Effect Improves symptoms and exercise tolerance in patients with pulmonary hypertension delays deterioration of condition. Pharmacokinetics Protein binding 60%. Metabolized in liver. Primarily excreted in urine minimal elimination in feces. Half-life 20-30 min. 

Smooth muscles and vascular smooth muscles Prostaglandins E2 and I2 cause arteriolar dilation in the systemic and pulmonary vascular beds. Prostaglandins and E2, as well as thromboxane B2, constrict the human umbilical cord. Leukotrienes C4 and D4, which release prostaglandin E, decrease peripheral vascular resistance. 

An ornipressiii infusion and adrenaline infusion plus water immersion (up to the neck, for a period of 5 hours) act on the lowered peripheral vascular resistance. (65) (s. p. 329) Low-dosage dopamine and prostaglandin or ANF infusions may have an effect on the increased renovascular resistance. (132)... 

Intravenous administration of indometacin increases blood pressure, coronary vascular resistance, and myocardial oxygen demands, decreasing coronary flow. A controlled short-term study showed that indometacin increased blood pressure in patients with mild untreated essential hypertension (SEDA-17, 108). In view of the increasing use of parenteral administration, the acute hemodynamic effects of indometacin may now occur more often, especially in the elderly (5). The mechanism is poorly understood, but apparently a direct action is exerted on the resistance vessels in various regions. This is probably independent of indometacin s action on prostaglandin formation. The chnical relevance is largely unknown, but other NSAIDs should probably be prescribed for patients with occlusive vascular diseases affecting the cerebral and/or coronary vessels. 

AGE may have the ability to mimic prostaglandin E2 (vasodilator), which could ultimately decrease peripheral vascular resistance. 

A role for endothelium-derived relaxing factor in renal vascular resistance and in glomerular and tubular function was first observed in the IPRK by Bhardwaj and Moore [198] and by Rademacher et al. [199-201]. Others have observed that manipulating nitric oxide can alter medullary oxygenation in the IPRK [109]. An increased endothelium-dependent vasodilator response to acetylcholine was observed in IPRK from cirrhotic rats [202]. Portal vein ligation also lowered renal vascular resistance that was not related to nitric oxide or prostaglandins, although increased nitric ox-... 

Studies of the pathophysiology of acute renal failure has classically considered both tubular and vascular mechanisms [227,228]. In vitro techniques isolating either the vascular or tubular components have been developed. For example, the use of isolated proximal tubules in suspension or in culture allows the study of tubular mechanisms of injury in the absence of vascular factors [229] [230]. There are both in vitro and in vivo models to study vascular injury in the kidney. In vitro models include the study of vascular smooth muscle cells or endothelial cells in culture. In this section, the in vivo methods to evaluate the renal micro-circulation will be discussed. This is of relevance as many nephrotoxins exert their deleterious effects through pharmacologic actions on the resistance vasculature with parenchymal injury occurring as a consequence of ischemia. In clinical practice nephrotoxins may cause prerenal azotemia as a result of increased renal vascular resistance. Nephrotoxins that cause acute renal failure on a vascular basis include prostaglandin inhibitors e.g. aspirin, non-steroidal anti-... 

Prostaglandins as antihypertensives have so far not materialized as first hoped. PGs of the E and A series are potent vasodilators, as is PGI2 (see below). They decrease vascular resistance and systemic blood pressure. PGEs work directly on smooth muscle to produce this effect. PGA and PGA2 decrease pressure in essential hypertension to normal levels, increase cardiac output, and lower peripheral resistance. Renal circulation also improves. 

Seeger, W., Wolf, H., Stabler, G., Neuhof, H. and Roka, L. (1982). Increased pulmonary vascular resistance and permeability due to arachidonate metabolism in isolated rabbit lungs. Prostaglandins, 23, 157—173... 

Zimmermann, B.G. (1978). Effect of meclofenamate on renal vascular resistance in early Goldblatt hypertension in conscious and anesthetized dogs. Prostaglandins, 15, 1027-1033... 

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