Angiotensin converting enzyme inhibition and calcium antagonism attenuate streptozotocin-diabetes-associated mesenteric vascular hypertrophy independently of their hypotensive action

J Hypertens. 1998 Jun;16(6):793-9. doi: 10.1097/00004872-199816060-00010.

Abstract

Objectives: To investigate the relative roles of angiotensin II, bradykinin, and calcium-dependent pathways in the genesis of mesenteric vascular hypertrophy in experimental diabetes.

Design: Streptozotocin-induced diabetic Sprague-Dawley rats were randomly allocated to these treatments for 24 weeks: no treatment; ramipril at a hypotensive dose; ramipril plus the bradykinin type 2 receptor blocker icatibant; icatibant alone; ramipril at a low dose; the angiotensin II type 1 receptor antagonist, valsartan; the dihydropyridine calcium antagonist, lacidipine; and the nondihydropyridine calcium antagonist mibefradil.

Methods: Systolic blood pressure was serially measured every 4 weeks by tail-cuff plethysmography. We assessed the vascular architecture in sections of mesenteric arteries obtained after in-vivo perfusion, which were stained with an antibody to alpha-smooth muscle actin.

Results: Both blood pressure and the mesenteric arterial wall: lumen ratio were reduced by administration of ramipril, at the high dose, either alone or in combination with icatibant, and also by valsartan. Treatment either with the low dose of ramipril or with the calcium antagonists lacidipine and mibefradil was associated with a decrease in the wall : lumen ratio of the mesenteric arteries without influencing blood pressure.

Conclusions: These findings demonstrate that blockade both of angiotensin II-dependent and of calcium-dependent pathways attenuates mesenteric vascular hypertrophy in experimental diabetes. Furthermore, the antitrophic effects of these antihypertensive agents may be independent of their hypotensive effects.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Angiotensin-Converting Enzyme Inhibitors / pharmacology*
  • Animals
  • Benzimidazoles / pharmacology
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Diabetes Mellitus, Experimental / physiopathology
  • Dihydropyridines / pharmacology
  • Hypertrophy
  • Male
  • Mesenteric Arteries / drug effects
  • Mesenteric Arteries / pathology*
  • Mibefradil
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology*
  • Peptidyl-Dipeptidase A / drug effects*
  • Peptidyl-Dipeptidase A / metabolism
  • Ramipril / pharmacology
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tetrahydronaphthalenes / pharmacology

Substances

  • Actins
  • Angiotensin-Converting Enzyme Inhibitors
  • Benzimidazoles
  • Calcium Channel Blockers
  • Calcium Channels
  • Dihydropyridines
  • Tetrahydronaphthalenes
  • lacidipine
  • Mibefradil
  • Peptidyl-Dipeptidase A
  • Ramipril