The effect of treatment with low dose ACE inhibitor and/or diuretic on coronary microvasculature in stroke-prone spontaneously hypertensive rats.
Angiotensin II is considered to have angiogenic properties. Nevertheless, several authors reported an increase in coronary capillary density after treatment with ACE inhibitors. The aim of the present study was to evaluate the effect of treatment with low doses of ACE inhibitor perindopril, low doses of the diuretic indapamide, or a combination of the two on microvascular structure in hearts from stroke-prone spontaneously hypertensive rats (SHR-sp). Young adult male SHR treated with indapamide (0.24 mg/kg/day), perindopril (0.76 mg/kg/day), or both were compared with untreated animals after 8 or 14 weeks of treatment. Survival of SHR-sp was significantly increased after treatment. Only perindopril alone or in combination with indapamide significantly decreased blood pressure and cardiac mass. Treatment also significantly increased capillary and myocyte densities but arteriolar density tended to decrease. External and internal diameters significantly increased in treated animals while arteriolar thickness remained the same. Thus, thickness in vessels of the same size was the greatest in untreated animals, followed by indapamide- and perindopril-treated rats with the thinnest walls in rats with combined treatment, and the treatment resulted in a significant increase in the lumen to wall ratio. Capillary and arteriolar growth responses in treated animals seem to indicate that the two are independently regulated processes. Treatment with indapamide alone at this dosage did not significantly influence most responses but in combination with perindopril it strengthened the effect of perindopril.
Rakusan
K
K
Faculty of Medicine, University of Ottawa, Ottawa, K1H 8M5, Canada.
Cicutti
N
N
Maurin
A
A
Guez
D
D
Schiavi
P
P
D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000473:pathology*; D007190:Indapamide / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D009206:Myocardium / Q000473:pathology; D020913:Perindopril / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR
D000806:Angiotensin-Converting Enzyme Inhibitors; D004232:Diuretics; D000804:Angiotensin II; D007190:Indapamide; D020913:Perindopril