Hypertension in experimental diabetes mellitus. Renin-prostaglandin interaction.

Abstract

SUMMARY To investigate mechanisms involved in the high incidence of hypertension in diabetes mellitus, the relationship between renin-angiotensin production and renal prostaglandin E 2 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 polyurla 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 E 2 synthesis in vitro were significantly lower in diabetic rats than in nondiabetic controls. Isoproterenol and prostaglandin E 2 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"' M) and prostaglandin E 2 (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 E 2 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 E 2 , the synthesis of which is also impaired in diabetes, 3) prostaglandin E 2 -induced renin release may operate independently from isoproterenol-induced renin release, and 4) impaired renal prostaglandin E 2 synthesis may contribute to the development of hypertension in the face of an unchanged prohypertensive renin-angiotensin II system. characteristic morphological and functional changes in the kidney. In addition, cardiovascular complications, including hypertension, atherosclerosis, and thrombotic disease, are more prevalent among diabetics than nondiabetics. Increased sensitivity of diabetic platelets to aggregating agents as well as increased diabetic platelet production of thrombox-

Diabetes mellitus, the Renin-Angiotensin System, and Angiotensin-Converting Enzyme Inhibition

“…Christlieb [29] found that severely hyperglycemic rats had lower levels of renin than normal or moderately hyperglycemic ani mals. This has been verified by others [30,31,33], Severe hyperglycemia will likely lead to volume depletion, which in turn should stimulate renin secretion. This does not occur, however.…”

Endothelin A Receptor Blockade Reduces Diabetic Renal Injury via an Anti-Inflammatory Mechanism

“…These changes may reflect the decline in cardiac function that arises during this stage of the disease (49). In contrast, some groups have reported no change (50,51) or an increase in BP in diabetic rats (52). It is possible that the discrepancies in these studies may be due to differences in the severity or the duration of diabetes, use of anesthetics, or method of BP measurement.…”

Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin-induced diabetes

“…Previous studies from our own laboratory have shown lower HR and reduced systolic blood pressure in conscious STZ-induced diabetic rats (44). However, a few studies from other laboratories have reported unchanged (5,6,24) or increased blood pressure in diabetic rats (22). Although the reasons for these discrepancies are not very clear, it is likely that differences in the duration of diabetes, use of anesthetics, and varied techniques employed for measurement of blood pressure may have contributed to the disparities in the observed results (25).…”