Decreased type VI adenylyl cyclase mRNA concentration and Mg2+-dependent adenylyl cyclase activities and unchanged type V adenylyl cyclase mRNA concentration and Mn2+-dependent adenylyl cyclase activities in the left ventricle of rats with myocardial infarction and longstanding heart failure

Objective: To address the effect of longstanding left ventricular (LV) hype rtrophy and failure on LV adenylyl cyclase (AC) gene expression, mRNA conce ntrations of the main cardiac AC isoforms were measured in the non-infarcte d area of LV from rats with myocardial infarction (MI), without (H) or with (F) LV failure, and in control (C) rats. Basal, GTP- and forskolin-stimula ted Mg2+ and Mn2+-dependent AC activities were also measured in F and C rat s. Methods: Two- acid six months after MI, steady-state AC mRNA concentrati ons were assessed by Northern blot analysis and RNase protection assay with isoform-specific cDNA and cRNA probes, respectively. AC activities were as sessed on LV microsomal fractions using standard procedures. Results: Types V and VI, and types IV and VII were the major and minor AC mRNA isoforms i n both the LVs of F and C rats. Two months after MI, no difference in LV ty pe V or VI mRNA to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA ra tios was observed in rats with H or F compared to C. Six months after MI, n o difference in LV type V mRNA concentration was observed between the three rat groups, whether this level was normalized to GAPDH, poly-(A(+)) or 18S RNAs. In contrast, a 35% decrease in the type VI mRNA to poly-(A(+)) RNA r atio and a 29% decrease in the type VI mRNA to 18S RNA ratio was observed o nly in rats with F compared to C (p<0.05 vs. C for the two comparisons). Tw o- and six months after MT, basal and forskolin-stimulated Mg2+-dependent A C activities were decreased by 30-35% in F rats compared to C (p<0.05), whe reas Mn2+-dependent activities were unchanged. Conclusion: Longstanding LV hypertrophy and failure resulting from MI in rats is not associated with al tered expression of the most abundant, type V, AC mRNA isoform, whereas tha t of type VI is decreased. The lack of change in Mn2+-dependent AC activiti es in the LV of F rats suggests that this decrease has no Mg2+-dependent ac tivities are related to alterations occurring upstream. functional conseque nce on overall AC activity and that decreased Mg (C) 1999 Published by Else vier Science B.V. All rights reserved.