Effects of Noradrenaline and Kcl on Peripheral Vessels in Doxorubicin Induced Model of Heart Failure Publisher



Ahmadiasl N¹ ; Rostami A² ; Mohammadi NM¹ ; Rajabi F³ Show Affiliations
Source: Pathophysiology Published:2002

Abstract

The purpose of the work presented here was to investigate the responses mediated by alpha-adrenoceptors and also contractility of vascular smooth muscle in large peripheral vessels following doxorubicin (DXR)-induced heart failure. Cardiac failure was induced by DXR injection. Thirty saline-treated (normal group) and 30 DXR-treated rabbits (1 mg/kg administered intravenously twice weekly for 8 weeks) were studied. Chronic heart failure was confirmed by echocardiography and later also by histopathology. The DXR-treated hearts were subdivided by ejection fraction >40 or <40 into non-failing (control) and failing (test) groups. Animals were sacrificed by overdose with pentobarbitone sodium (i.v. injection). Arteries and veins were carefully removed with as little connective tissue as possible and placed in cold physiological salt solution. The arterial and venous rings were mounted in 10 ml isolated organ baths, maintained at 37°C and gassed with 95% O2 plus 5% CO2. The rings were then placed under different resting tensions. After initial application of tension tissues were left to equilibrate for a 60-min period. Then all preparations were contracted with KCl (Krebs solution, Na free and high KCl, 125 mM) and allowed to contract for 5-10 min. Following complete washout with normal Krebs, an additional 30 min equilibration period was allowed. Then cumulative concentration-response curves to noradrenaline (NA) obtained by increasing the concentration of the agonist in half-log increments. In contraction responses to NA the renal artery and aorta were the most sensitive preparations (pD2 values: 5.75 and 5.36, respectively). Compared with control, in DXR-treated rabbits, maximum response (Emax) of NA was not modified in the aorta; renal and saphenous arteries, renal and saphenous veins, whereas it was significantly lower in the vena cava. Compared with control rabbits, in DXR-treated rabbits the pD2 of NA was significantly increased in the thoracic aorta whereas there was no significant difference between groups in the other studied vessels. Contraction to KCl showed no significant difference between two groups. These results suggest that the sympathetic regulation of vascular contraction is impaired by DXR-induced heart failure through reduction in the alpha-adrenoceptors. © 2002 Elsevier Science Ireland Ltd. All rights reserved.