Nonhypotensive dose of beta-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure.
Renal failure causes sympathetic overactivity and inadequate capillary growth in response to cardiomyocyte hypertrophy in experimental renal failure, as well as in uremic patients. In nonuremic animals, sympathetic overactivity was shown to suppress capillary growth. The purpose of this study was to examine whether blockade with alpha- and beta-adrenoblockers ameliorates the capillary deficit that was documented in the hearts of rats with moderate renal failure. Male Sprague-Dawley rats, 3 days after surgical ablation [subtotal nephrectomy (SNX)] or sham operation (sham), were treated with phenoxybenzamine, metoprolol, or a combination of both: After 12 weeks, the hearts were investigated using morphometric and stereologic techniques. The length density of myocardial capillaries was lower (p<0.05) in untreated SNX than in sham (2,786+/-372 vs 3,397+/-602 mm/mm3); the decrease was abrogated by metoprolol (3,305+/-624 mm/mm3), but not by phenoxybenzamin (2,628+/-480 mm/mm3). The intercapillary distance increased (p<0.05) in SNX (20.5+/-1.5 microm) and tended to be lower after metoprolol treatment (19.0+/-1.9 microm). The media area of intramyocardial arterioles was significantly higher in untreated SNX (1,158+/-1,343 vs 686+/-771 microm2 in sham). Metoprolol in nonhypotensive doses prevents the capillary deficit in the hearts of rats with moderate renal failure and presents an argument for an important role of sympathetic overactivity in the genesis of the capillary deficit in moderate chronic renal insufficiency.
Amann
Kerstin
K
Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, 91054 Erlangen, Germany. kerstin.amann@patho.imed.uni-erlangen.de
Hofstetter
Jürgen
J
Câmpean
Valentina
V
Koch
Andreas
A
Gross
Marie-Luise
ML
Veelken
Roland
R
Ritz
Eberhard
E
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; 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* / Q000473:pathology; D019332:Endothelin-1 / Q000037:antagonists & inhibitors; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D010643:Phenoxybenzamine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000319:Adrenergic beta-Antagonists; D019332:Endothelin-1; D010643:Phenoxybenzamine; D008790:Metoprolol