Desensitization of adenylate cyclase and increase of Gi alpha in cardiac hypertrophy due to acquired hypertension.

Abstract

The present study investigated whether reduced adenylate cyclase activity and an increase in inhibitory guanine nucleotide binding proteins (Gi alpha), which have been observed in the failing human heart, already occur in myocardial hypertrophy before the stage of heart failure. In membranes of hypertrophic hearts from rats with different forms of experimentally induced hypertension without heart failure (one-kidney, one clip rats, deoxycorticosterone-treated rats, and rats with reduced renal mass), basal as well as isoprenaline-, 5'-guanylylimidodiphosphate-, and forskolin-stimulated adenylate cyclase activity was reduced. The activity of the catalyst was depressed in deoxycorticosterone but unchanged in one-kidney, one clip and reduced renal mass compared with controls. The number of beta-adrenergic receptors was similar in all groups. Radioimmunological quantification of Gi alpha proteins revealed an increase by 73% in one-kidney, one clip, 67% in reduced renal mass, but only 20% in deoxycorticosterone compared with sham-operated, age-matched control rats. The increase of Gi alpha was accompanied by smaller changes of pertussis toxin-induced [32P]ADP-ribosylation of a 40-kd membrane protein. It is concluded that Gi alpha contributes to the reduced adenylate cyclase activity in cardiac hypertrophy in one-kidney, one clip and reduced renal mass and to a smaller extent in deoxycorticosterone. It is suggested that an enhanced expression of Gi alpha could occur not only in severe heart failure but also in cardiac hypertrophy and could, therefore, contribute to myocardial depression and progression of disease in heart failure. In addition, Gi alpha might represent an important regulatory mechanism for cardiac adenylate cyclase activity and thus, might play an important role in various cardiac diseases.

• Authors: M Böhm, P Gierschik, A Knorr, K Larisch, K Weismann, E Erdmann
• Journal: Hypertension (Dallas, Tex. : 1979) (Hypertension) Vol. 20 Issue 1 Pg. 103-12 (Jul 1992) ISSN: 0194-911X [Print] United States
• PMID: 1319958 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Adrenergic, alpha
• GTP-Binding Proteins
• Adenylyl Cyclases

Topics

• Adenylyl Cyclases (metabolism)
• Animals
• Blood Pressure
• Cardiomegaly (etiology, metabolism)
• GTP-Binding Proteins (metabolism)
• Hypertension (complications, physiopathology)
• Myocardium (metabolism)
• Rats
• Rats, Inbred Strains
• Receptors, Adrenergic, alpha (metabolism)