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(Hypertension. 1995;25:962-970.)
© 1995 American Heart Association, Inc.

Articles

Treatment in Hypertensive Cardiac Hypertrophy, II

Postreceptor Events

Michael Böhm; Claudia Gräbel; Markus Flesch; Andreas Knorr; Erland Erdmann

From the Klinik III für Innere Medizin der Universität zu Köln and Bayer AG (A.K.), Wuppertal, Germany.

Abstract We investigated the effect of pharmacological treatment with captopril, nitrendipine, and captopril plus nitrendipine on myocardial heterologous adenylyl cyclase desensitization and the underlying postreceptor defects in spontaneously hypertensive rats (SHR). In myocardial membranes from SHR, stimulation of adenylyl cyclase with guanylylimidodiphosphate (P<.001) and forskolin (P<.05) was significantly reduced, whereas no difference with forskolin was obtained in the presence of manganese chloride. Reconstitution of G_s into G_s-deficient S49 cyc^- mouse lymphoma cells revealed no difference between SHR and control rats. In contrast, pertussis toxin labeling of G_i was significantly increased in SHR. The reduction of adenylyl cyclase in SHR was abolished after pertussis toxin treatment of membranes. Treatment with captopril, nitrendipine, or both reduced G_i and increased guanylylimidodiphosphate-stimulated adenylyl cyclase activity in SHR. In summary, heterologous adenylyl cyclase desensitization due to an increase of G_i but in the presence of an unchanged activity of G_s or the catalyst occurs in SHR. This alteration, which could contribute to the progression of contractile dysfunction by producing adrenergic subsensitivity, is sensitive to pharmacological treatment most likely because of a reduction of sympathetic activity.

Key Words: hypertension, essential • heart hypertrophy • heart failure, congestive • rats, inbred SHR • adenylyl cyclase • pertussis toxins • angiotensin-converting enzyme inhibitors • calcium channel blockers

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