Renal Prostaglandins

Abstract

The renal prostaglandins PGA₂ and PGE₂ possess potent antihypertensive and vasodepressor activity. The mechanism of blood pressure lowering effect is through peripheral arteriolar dilation with a fall in total peripheral resistance. PGA unlike PGE escape degradation by the lung and thus could circulate as antihypertensive hormones. Since plasma PGA levels rise in humans on a low sodium intake, it has been postulated that the beneficial effects of a low sodium diet in some hypertensives may be the result of an increase in peripheral vasodilating PGA. Support that plasma PGA may be a regulator of systemic blood pressure is also derived from the fact a PGA-secreting renal tumor was associated with a fall in blood pressure and a rise in plasma PGA in a previously hypertensive woman. The removal of the tumor resulted in a return of blood pressure to elevated levels and a concomitant fall in PGA. Recently, a number of human patients with essential hypertension have been infused with PGA₁ and PGA₂. It was observed that there was an initial increase in renal blood flow, sodium and water excretion which was associated with no change in the elevated blood pressure. When blood pressure ultimately fell, there was a return of renal blood flow, sodium and water excretion to preinfusion levels. It would appear that PGA compounds act as ‘ideal’ antihypertensive agents since they favorably effect renal resistance, sodium and water homeostasis, plasma volume, total peripheral resistance, blood pressure and indirectly cardiac output through baroreceptor stimulation, all factors known to be important in etiology in human hypertension.

Reproductive failure and reduced blood pressure in mice lacking the EP2 prostaglandin E2 receptor

“…PGE 2 also has potent effects on the cardiovascular system. A role for PGE 2 in blood pressure homeostasis has been recognized for years, but these actions are complex, involving regulation of vascular tone and sodium balance (17). To examine the role of the EP2 receptor in blood pressure regulation, we measured systolic blood pressure in conscious Ep2 -/-animals.…”

Secretion of prostaglandins as bone-resorbing agents by renal cortical carcinoma in culture

“…2 (top) shows the PGE level in pooled culture medium from the same experiment. (Lee and Attallah, 1975) and 1,25-(OH)2D3 (Lawson et al, 1971) are produced in normal kidney, and there is an inicidence, of uinknown frequency, of secretion of PTH by renal cortical carcinoma (Buckle, McMillan anid Mallinson, 1970;Greenberg et al, 1973 writh hypercalcaemia (Benson et al, 1974) it has beeni exclutded as a causative agent in many other hyperealcaemic patients free from skeletal metastases (Powell et al, 1973). Although cyclie AMP is involved in the action of PTH on bone (Chase and Autrbach, 1970) Prostaglandins are potenlt bone-resorbitg agents in vitro (Klein and Raisz, 1970) and are associated, probably as causative agents, with hypercalcaemia of malignancy (Tashjian et al, 1972;Powles et al, 1973;Bennett et al, 1975;Dowsett et al, 1976).…”

Loss of the PGE1 requirement for MDCK cell growth associated with a defect in cyclic AMP phosphodiesterase

“…Also, unlike classic hormones, the effects of particular prostaglandins may vary in different cell types and are not necessarily mediated by cyclic adenylic acid (cyclic AMP) (Samuelsson et al, 1978). The kidney produces large quantities of prostaglandins which affect a number of renal functions (Lee and Attallah, 1977). Consequently, the mechanisms by which prostaglandins affect renal cells are of particular interest.…”