Remodeling of mesenteric resistance arteries in the genetically hypertensive (GH) rat; effects of treatment with an ACE inhibitor, an angiotensin II receptor antagonist and a calcium antagonist

Ledingham, JM: Department of Pharmacology,Otago University Medical School, New Zealand

Laverty, R: Department of Pharmacology,Otago University Medical School, New Zealand

In the GH rat strain BP is raised from an early age and cardiovascular structure is altered. To observe the effects of different drug classes on vascular structure we treated GH from age 4-10 weeks with enalapril, losartan or felodipine and measured effects on BP, left ventricular (LV) mass and on structural remodeling of mesenteric resistance arteries (MRA).

The mesenteric arcade was fixed by perfusion, 2nd order branches of mesenteric arteries were embedded in Technovit and stained sections analysed using stereological methods.

Enalapril and losartan significantly lowered BP and LV mass to normal levels. Felodipine treatment lowered BP and LV mass significantly but they were not normalised. In MRA, enalapril and losartan reduced the ratio of media width/lumen diameter to below normal by a large increase in lumen diameter (eutrophic outward remodeling), while felodipine lowered the ratio to normal through significant media reduction as well as increased lumen size (hypotrophic outward remodeling). In felodipine treated GH, structural changes in MRA occurred even when BP was not normalised suggesting that they are not wholly dependent on BP. Since both enalapril and losartan treatment led to the same structural remodeling the structural changes are probably due to blocking of angiotensin rather than any bradykinin effect.

Contact: janet.ledingham@stonebow.otago,ac.nz

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