Nonhypotensive dose of β-adrenergic blocker ameliorates capillary deficits in the hearts of rats with moderate renal failure

Abstract

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.

Chronic Kidney Disease (CKD) as a Systemic Disease: Whole Body Autoregulation and Inter-Organ Cross-Talk

“…However, this hypothesis-generating study did not contemplate a control procedure (sham renal denervation) and was too small to allow sensible conclusions on the value of renal denervation for hypertension control and attenuation of CKD progression in these patients. Nonetheless, this study is in keeping with data in experimental models in the rat showing that interventions that reduce sympathetic activity mitigate renal damage in the same models [20,21]. …”

Cardiovascular Problems on Hemodialysis

“…In models of impaired renal function, ␤ receptor blockade attenuates progression even when given on top of renin-angiotensin system blockade (46). In experimental studies, ␤ blockade affects cardiac function and ameliorates even one facet of uremic cardiomyopathy: the capillary deficit (47).…”

Cross-Talk between the Kidney and the Cardiovascular System

“…Clarification of these points requires further experiments. Intervention trials also gave some hints as to the pathomechanisms underlying the decrease in cardiac capillary supply: It was prevented by the central sympatholytic agent moxonidine (65) by selective and nonselective ET receptor blockers (66,71) and in recent studies also by the ␤ blocker metoprolol (72). In contrast, treatment with the calcium channel blocker nifedipine or the ACE inhibitor ramipril or correction of anemia with rhEPO did not affect myocardial capillary density.…”