ARGININE VASOPRESSIN GENE-EXPRESSION IN CHRONIC CARDIAC-FAILURE IN RATS

Arginine vasopressin (AVP) is known to be increased in patients and experimental animals with chronic cardiac failure (CCF). The importance of an increase in biosynthesis of AVP in the hypothalamus has, however, not heretofore been investigated and is the purpose of the present study. CCF secondary to infarction of myocardial tissue was induced by ligation of the left anterior descending coronary artery and sham operated animals served as controls. Four weeks later hypothalamic AVP mRNA was determined by solution hybridization using sense and anti-sense strand RNA. The blood pressure was lower in CCF than sham animals (131.2 ± 3.1 vs. 112.8 ± 4.0 mm Hg, P < 0.05) and the total heart, and right and left ventricle weights were significantly higher in CCF rats. Plasma AVP was higher in CCF (sham 6.78 ± 0.30; CCF 11.46 ± 0.64 pg/ml, P < 0.001) and plasma atrial natriuretic peptide was also higher in CCF than sham animals (205 ± 36 vs. 554 ± 56 pg/ml, P < 0.001). The AVP mRNA in hypothalamus was significantly higher in CCF than sham animals (55.5 ± 3.7 vs. 95.9 ± 4.0 pg/μg total RNA, P < 0.001). There was no difference in β-actin mRNA in the hypothalamus of sham and CCF rats, indicating that the AVP-mRNA increase was specific in CCF. These results therefore demonstrate that increased AVP biosynthesis in the hypothalamus, in addition to release of the hormone from the posterior pituitary, may occur in CCF.