Effects of enalapril, losartan, and verapamil on blood pressure and glucose metabolism in the Cohen-Rosenthal diabetic hypertensive rat.
We undertook the present study to examine the effect of the angiotensin-converting enzyme inhibitor enalapril, the angiotensin II antagonist losartan, and calcium antagonist verapamil on systolic pressure and spontaneous blood glucose levels in rats from the Cohen-Rosenthal diabetic hypertensive strain. Genetic hypertension and diabetes developed in this strain after crossbreeding of Cohen diabetic and spontaneously hypertensive rats. The new rat strain was fed their usual copper-poor sucrose diet, which is essential for the development of this model, and for 4 weeks received either enalapril, losartan, or verapamil. Systolic pressure was reduced significantly compared with controls in all treated groups. Chronic treatment with enalapril or verapamil, but not with losartan, succeeded in lowering spontaneous blood glucose, indicating improved diabetic control. Data suggest that angiotensin-converting enzyme inhibition by enalapril, but not angiotensin II antagonism by losartan, can improve glucose metabolism in addition to its hypotensive effect in a genetic diabetic hypertensive rat strain. This confirms that the drop in glucose with converting enzyme inhibition is highly dependent on bradykinin accumulation. Data further suggest that calcium channel blockade by verapamil can also improve glucose metabolism. The question remains whether the reduction in glucose by verapamil was a result of inhibition of glucogenesis.
Rosenthal
T
T
Chorley Institute of Hypertension, Chaim Sheba Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Hashomer, Israel.
Erlich
Y
Y
Rosenmann
E
E
Cohen
A
A
D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D001786:Blood Glucose; D002121:Calcium Channel Blockers; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D004656:Enalapril; D014700:Verapamil; D005947:Glucose; D019808:Losartan