Hyperinsulinemia and Insulin Resistance in Hypertension: Differential Effects of Antihypertensive Agents

Abstract

Both hypertension and diabetes mellitus are multifaceted dynamic expressions of pathophysiological disequilibrium that are closely related with and even intermingled by a number of common factors. Hyperinsulinaemia and insulin resistance may be possible links between hypertension and diabetes mellitus. While working on the effect of different antihypertensive agetns in several animal models of simultaneously occurring diabetes-mellitus and hypertension it was found that most antihypertensives prevented streptozotocin (STZ)-induced hypertension in rats. Hydralazine, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers (CCB) and clonidine prevented STZ-induced cardiomyopathy, hyperiipidaemia and glucose tolerance. It was further demonstrated that atenolol produced many unfavourable effects like hyperlipidaemia and decreased cardiac functions. We also used other animal models of simultaneously occurring diabetes-mellitus and hypertension such as genetically hypertensive or spontaneously hypertensive (SH), Deoxycorticosterone acetate (DOCA)-hypertensive and neonatal streptozotocin-induced NIDDM rats. Results of our studies suggest that SH, neonatal STZ-induced NIDDM, and fructose hypertensive rat models may be considered as models for insulin resistance - the concept that has come into limelight in recent years. DOCA may have some influence on glucose homeostasis and insulin sensitivity and some sort of counteraction to STZ-induced cardiovascular and metabolic changes occur with DOCAV. Hence, it may not be considered as an ideal model to study the metabolic and cardiovascular complications of hypertension associated with diabetes-mellitus. Among ACE inhibitors, perindopril, spirapril, and among calcium channel blockers (CCB) used in our study amlodipine and nifedipine were found to produce an increase in insulin sensitivity. Enalapril, ramipril, lisinopril and nitrendipine failed to alter insulin sensitivity as far as the glycaemic control is concerned. Extension of the results of these experiments to the clinical practice substantiated many of the findings and a good correlation between results obtained from experimental studies and clinical data was found.

Key Words:

• Diabetes mellitus
• hypertension
• insulin resistance
• antihypertensives
• calcium channel blockers
• ACE inhibitors