Defective synthesis of vasodilator prostaglandins in the spontaneously hypertensive rat.
Results of in vitro studies performed in different laboratories have led to the hypothesis that in spontaneously hypertensive rats (SHR), the biosynthesis of the vasodilator prostaglandins (PG) I2 and E2 increases secondarily to the rise in the arterial pressure, as a protective mechanism for reducing the severity of hypertension. In this study, this hypothesis was tested in vivo in SHR and control Wistar-Kyoto (WKY) rats under normal and high sodium diets. The 24-hour urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha, an endogenous metabolite of PGI2, was used as an index of the total production of PGI2 in the rats, whereas the urinary levels of PGE2 were used as an index of the renal production of this prostaglandin. Urinary levels of PGE2, obtained at 10 and 12 weeks of age, were always lower in SHR than in WKY rats and were not influenced by dietary sodium. In WKY and SHR on normal diets, the urinary levels of 2,3-dinor-6-oxo-PGF1 alpha did not differ significantly. However, the chronic administration of a high sodium diet (5.9% NaCl) was accompanied by a significant and sustained rise in the urinary excretion of 2,3-dinor-6-oxo-PGF1 alpha in the order of 30% to 50% in WKY but not in SHR, a finding similar to that in Dahl rats. These results point to the existence of an impaired capacity in SHR to synthesize vasodilator prostaglandins in vivo, contrary to the situation prevailing in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
D015121:6-Ketoprostaglandin F1 alpha / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D004032:Diet; D015232:Dinoprostone; D011464:Epoprostenol / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D011458:Prostaglandins E / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D012964:Sodium / Q000494:pharmacology; D014664:Vasodilation
D011458:Prostaglandins E; D015121:6-Ketoprostaglandin F1 alpha; C028290:2,3-dinor-6-ketoprostaglandin F1alpha; D012964:Sodium; D011464:Epoprostenol; D015232:Dinoprostone