Hypertension in experimental diabetes mellitus. Renin-prostaglandin interaction.
To investigate mechanisms involved in the high incidence of hypertension in diabetes mellitus, the relationship between renin-angiotensin production and renal prostaglandin E2 synthesis was studied in rats 1 week after diabetes mellitus had been induced by streptozotocin injection. The diabetic rats became hypertensive, although plasma renin activity did not increase despite the plasma volume contraction resulting from polyuria and natriuresis. Subcutaneous insulin injection resulted in a marked increase in plasma renin activity, while more rigid control of diabetes mellitus achieved by constant insulin infusion decreased blood pressure. Cortical renin content and renin release as well as papillary prostaglandin E2 synthesis in vitro were significantly lower in diabetic rats than in nondiabetic controls. Isoproterenol and prostaglandin E2 stimulated renin release in controls, while diabetic rats responded only to isoproterenol. Insulin infusion by pump reversed these abnormalities. An additive effect of a maximum dose of isoproterenol (10(-5) M) and prostaglandin E2 (10(-4) M) on renin release was observed in nondiabetic controls and in diabetic rats treated with insulin pump, but not in untreated diabetic rats. The results suggest that 1) renal renin release and prostaglandin E2 synthesis in diabetes mellitus are insulin dependent, 2) inappropriately lower plasma renin activity in diabetes mellitus may be attributed to a diminished renal renin pool and a lack of renin release in response to renal prostaglandin E2, the synthesis of which is also impaired in diabetes, prostaglandin E2-induced renin release may operate independently from isoproterenol-induced renin release, and impaired renal prostaglandin E2 synthesis may contribute to the development of hypertension in the face of an unchanged prohypertensive renin-angiotensin II system.
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D015232:Dinoprostone; D004347:Drug Interactions; D006706:Homeostasis; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism; D007332:Insulin Infusion Systems; D007545:Isoproterenol / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D008297:Male; D011458:Prostaglandins E / Q000096:biosynthesis / Q000378:metabolism* / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood / Q000378:metabolism*; D012084:Renin-Angiotensin System
D001786:Blood Glucose; D011458:Prostaglandins E; D012083:Renin; D015232:Dinoprostone; D007545:Isoproterenol