In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 91, No. 11 ( 2002-11-29), p. 1056-1062
Abstract:
Treatment of rats with monocrotaline (MCT) leads to pulmonary hypertension, right ventricular (RV) hypertrophy, and finally to RV heart failure. This is associated with characteristic changes in right ventricular β-adrenoceptors (β-AR), neuronal noradrenaline transporter (NAT) density and activity (uptake 1 ), and G protein–coupled receptor kinase (GRK) activity. This study aimed to find out factors that determine β-AR, uptake 1 , and GRK changes. Thus, 6-week-old rats were treated with 50 mg/kg MCT subcutaneous or 0.9% saline. Within 13 to 19 days after MCT application (group A), RV weight (222±6 versus 147±5 mg) and RV/left ventricular (LV) weight ratio (0.42±0.01 versus 0.29±0.01) were significantly increased, whereas plasma noradrenaline, RV β-AR density, RV NAT density and activity, and RV GRK activity were not significantly altered. Twenty-one to twenty-eight days after MCT (group B), however, not only RV weight (316±4 versus 148±2 mg) and RV/LV weight ratio (0.61±0.01 versus 0.3±0.01) were markedly increased but also plasma noradrenaline (645±63 versus 278±18 pg/mL); now, RV β-AR density (13.4±1.3 versus 26.5±1.1 fmol/mg protein), RV NAT density (50.9±11.3 versus 79.6±2.9 fmol/mg protein), and RV NAT activity (65.4±7.4 versus 111.8±15.9 pmol [ 3 H]-NA/mg tissue slices/15 min) were significantly decreased and RV-membrane GRK activity (100±15 versus 67±6 [ 32 P]-rhodopsin in cpm) significantly increased. LV parameters of MCT-treated rats were only marginally different from control LV. We conclude that in MCT-treated rats ventricular hypertrophy per se is not sufficient to cause characteristic alterations in the myocardial β-AR system often seen in heart failure; only if ventricular hypertrophy is associated with neurohumoral activation β-ARs are downregulated and GRK activity is increased.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/01.RES.0000045088.59360.B7
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2002
detail.hit.zdb_id:
1467838-X
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