Myocardial changes after spironolactone in spontaneous hypertensive rats. A laser scanning confocal microscopy study.
The present study aims to objectivate by laser scanning confocal microscopy, the cardiac structure of the spontaneously hypertensive rats (SHR) treated with different doses of spironolactone, either alone or in combination with an angiotensin converting enzyme inhibitor or with a calcium channel blocker. Thirty SHRs were divided into six groups and treated during 13 weeks as follows: control, spironolactone (5, 10 and 30 mg/kg/day), spironolactone + enalapril and spironolactone + verapamil. Spironolactone action on the SHR blood pressure (BP) was dose-dependent. The cardiac hypertrophy was affected by the treatment with spironolactone (high dose) or a combination of spironolactone and Enalapril. The myocardial structure was less affected by the spironolactone monotherapy (at all doses) showing hypertrophied cardiac myocytes, focal areas of the reactive fibrosis, inflammatory infiltrate. The treatment with spironolactone in combination with enalapril or verapamil prevented these alterations. In conclusion, the monotherapy with spironolactone had only a limited effect in the preservation of the myocardial structure and in the attenuation of the interstitial fibrosis in SHRs, even after high dose. This action on the myocardium is more efficient when the spironolactone (even in medium dose) was associated with enalapril or verapamil.
Pereira
Leila Maria Meirelles
LM
Laboratory of Morphometry & Cardiovascular Morphology, Biomedical Centre, Institute of Biology, State University of Rio de Janeiro, Brazil.
Mandarim-de-Lacerda
C A
CA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D009206:Myocardium / Q000473:pathology*; D051381:Rats; D011918:Rats, Inbred SHR; D013148:Spironolactone / Q000494:pharmacology* / Q000627:therapeutic use; D013223:Statistics as Topic; D014700:Verapamil / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002121:Calcium Channel Blockers; D000451:Mineralocorticoid Receptor Antagonists; D013148:Spironolactone; D004656:Enalapril; D014700:Verapamil