Stimulation of Renal Prostaglandins by Pressor Hormones in Man: Comparison of Prostaglandin E2 and Prostacyclin (6 Keto prostaglandin F1 )

The effect of vasoconstrictive agonists and their nonpressor analogs on renal prostaglandin production was investigated in normal subjects maintained on constant diets. Arginine vasopressin (AVP), 10 U, desamino-d arginine vasopressin (dDAVP), 4 micrograms, angiotensin II (AII), 5 ng/kg . min, des-Asp angiotensin II (AIII), 5 ng/kg . min, norepinephrine (NE), 0.1 microgram/kg . min, and NE plus phenoxybenzamine (PHB), 0.8 mg/kg, were administered on separate days. Prostaglandin E2 (PGE2) and the stable prostacyclin metabolite, 6 keto prostaglandin F1 alpha were measured in 4-h urine collections by procedures with high resolution chromatography and RIA using highly specific antisera. AVP and dDAVP similarly reduced urine volume and increased urine osmolality. AII, AIII, NE, and NE + PHB did not alter basal urine volume, osmolality, creatinine, or electrolyte excretion. Blood pressure was similarly increased by AII and NE infusions (23 +/- 3 vs. 19 +/- 2 (SE) mm Hg). AVP and AII increased only PGE2 excretion (61 +/- 8 to 151 +/- 34 ng/4 h for AVP, and 38.7 +/- 7 to 75 +/- 19 ng/4 h for AII, P less than 0.05). The nonpressor analogs, dDAVP and AIII, had no effect on urinary prostaglandin excretion. In contrast, NE increased both PGE2 (from 38.7 +/- 7 to 74.5 +/- 12 ng/4 h, P less than 0.02) and 6 keto prostaglandin F1 alpha (from 34.6 +/- 8 to 56.1 +/- 9 ng/4 h, P less than 0.02). alpha-Blockade with PHB totally abolished the NE-induced systemic pressor and prostaglandin stimulatory effect. These data suggest that renal PGE2 and prostacyclin are not altered in parallel by vasoactive stimuli. PGE2 appears to be released in response to agents that induce renal vasoconstriction and reduced renal blood flow whereas renal prostacyclin excretion is stimulated by an adrenergic agonist via alpha-receptor activation and not vasoconstriction per se.