Effects of prostaglandin E2, I2 and F2.ALPHA. on systemic and renal hemodynamics, renal function and renin secretion in anesthetized dogs.

Abstract

Abstract-Effects of intrarenal-arterial (i.r.a.) and intravenous (i.v.) infusions of PGE2, 12 and Fza on systemic blood pressure (BP), heart rate (HR), renal blood flow (RBF), urine volume (UV), renal function and plasma renin activity (PRA) of the renal venous blood (RVPRA) were investigated. A dose-dependent fall in BP was observed with PGE2 and 12 and was accompanied by a tachycardia (PGE2<12, i.r.a.<i.v.). PGEZ and 12 induced increases in RBF and UV in a roughly dose-dependent manner (PGE2> 12, i.r.a.>i.v.), however, antidiuresis was observed with the highest intravenously given dose of PGI2 (300 ng/kg/min) such being ascribed to a pronounced hypotension. Changes in electrolyte excretion induced by PGE2 and 12 were similar to the pattern of those in RBF or UV. Neither PGE2 or 12 produced any significant changes in the glomerular filtration rate (GFR). The diuretic effect of PGE2 and Fza correlated with osmolar clearance (Cos,71) (r-0.89, p<0.01 ; r=0.55, p<0.01) and free water clearance (Cixzo) (r=0.52, p<0.01 ; r=0.83, p<0.01), whereas that of PGI2, only with Cosm (r=0.74, p<0.01).PGF2a produced the weakest changes in the parameters described above. PGE2 and 12 (30 ng/kg/min, i.r.a.), but not PGF2a, produced a significant elevation of RVPRA without any significant change in BP. These findings suggest that PGE2 plays a primary role in the kidney, whereas PG12 is important in the regu lation of the systemic circulation, and that PGE2, 12 and F2a all have different modes of action in producing diuresis. Both PGE2 and 12 may participate in the control of renin secretion. PGI2 (prostacyclin; originally called PGX) was first labelled as an unstable substance that inhibited platelet aggregation (1) and has been shown to be synthesised in arteries, veins, heart, kidney and other tissues in different species including humans (1-5). This PG has a different biological property from PGE2, since PGI2 survives the inactivation in the lung (6), while PGE2 is largely inactivated during a single passage through the lung (7), and is thought to be a circulating hormone. PGI2 causes vasodilatation in rats (8) and dogs (9), and has a vasodepressor action of approximately 4-8, 2 and 10 times greater than that of PGE2 in rats, rabbits (10) and dogs (11), respectively. The renal action of PGI2 has, however, been less intensely investigated. There is no systematic comparison of the renal effects of PGE2, 12 and F2,1 in extensive dose ranges, and to my knowledge, there are no reports dealing with the renal effects of PGI2 in relation to its systemic and renal hemodynamic effects.In the present study, an attempt was made to delineate the direct action of PG's on the excretory function of the kidney, differentiating it from hemodynamic intervention. For that purpose, the effects of PGE2, 12 and F2, on systemic and renal hemodynamics and renal

Stimulation of diuresis and natriuresis by renomedullary infusion of a dual inhibitor of fatty acid amide hydrolase and monoacylglycerol lipase

“…The results of our study support the idea that anandamideinduced diuresis occurs without FAAH-mediated hydrolysis to release arachidonic acid, the precursor to PGE 2 , the major renal prostaglandin. In the kidneys, PGE 2 acts as a paracrine hormone to inhibit sodium reabsorption, promotes diuresis, and acts as a vasodilator in the renal vasculature (13). The diuretic effect of IDFP, an inhibitor of FAAH, was accompanied by decreased urinary PGE 2 , providing direct support for the PGE 2 independence of this effect.…”

Diuretic, Natriuretic, and Vasodepressor Activity of a Lipid Fraction Enhanced in Medium of Cultured Mouse Medullary Interstitial Cells by a Selective Fatty Acid Amide Hydrolase Inhibitor

“…Noted for their high content of arachidonic acid in lipid granules and the presence of high constitutive COX levels, interstitial cells were demonstrated to synthesize and secrete prostaglandin E 2 in response to stimulation of receptors on their cell surface for vasopressor hormones such as angiotensin (Zusman and Keiser, 1977a). Prostaglandin E 2 is a vasodilator as well as a diuretic and natriuretic (Hashimoto, 1980). To our knowledge, medullipin is the only other major antihypertensive lipid proposed to be produced and released by medullary interstitial cells (Brooks et al, 1994;Cowley, 1994).…”