In six-week old Wistar-rats a single monocrotaline (MCT-) application (50 mg/kg MCT, s.c.) leads within 28 days to pulmonary hypertension, right ventricular (RV) hypertrophy (RVH) and RV failure (RVF) associated with characteristic changes in: plasma noradrenaline (pNA) content, neuronal noradrenaline transporter (NAT) density and activity (uptake₁) and ß-adrenoceptor (ßAR) density (Leineweber et al. 2002). The aim of the study was to investigate whether carvedilol (CARV), a non-selective ß-AR antagonist with additional -AR antagonistic effects, influences the development of MCT-induced RVH and whether CARV might affect the alterations in the ß-AR-System normally associated with RVH and RVF.Thus, saline (S)- and MCT-treated rats were randomly selected and either treated orally with 3.5 mg CARV/kg body weight (S-C, MCT-C) or with placebo (S-P, MCT-P) from the 3^rd until the 28^th day after MCT-application. We assessed in right (RV) and left ventricles (LV) ßAR density (by (-)-[¹²⁵I]-iodocynao-pindolol binding in fmol/mg protein), NAT density (by [³H]-nisoxetine binding in fmol/mg protein) and activity (by accumulation of [³H]-NA into tissue slices in pmol NA/mg tissue slices/15 min at 25 nM [³H]-NA) and pNA (per puncture of the ophthalmic venous plexus via HPLC in pg/ml). Results are summarized in Table 1.

Table1: Values are means±S.E.M of 16 animals in each group with ^a)p<0.05 vs. S-P; ^b)p<0.05 vs. S-C
and ^c)p<0.05 vs. MCT-P.

Conclusion: Although CARV significantly increase NAT-density/activity and although the chamber-specific RVH-associated reduction of the ßAR-density is attenuated, CARV had NO influence on the development and progression of MCT-induced RVH in rats.

Leineweber et al. (2002) Circ Res. 91: 1056-62.