Key result
Renovascular hypertension diminished the expression of Kv4.2 and Kv4.3 mRNAs by >50% in rat ventricles, an effect blocked by chronic captopril administration.
Why the study?
Does renovascular hypertension alter the expression of cardiac voltage-gated K+ channel subunit genes in rats, and does captopril prevent these changes?
Does renovascular hypertension alter the expression of cardiac voltage-gated K+ channel subunit genes in rats, and does captopril prevent these changes?
Effect estimate: >50% reduction
Renovascular hypertension causes specific reductions in Kv4 subfamily channel mRNA expression in rat ventricles, an effect prevented by captopril and likely mediated by increased cardiac afterload.
These rat findings suggest afterload-sensitive Kv4 remodeling; leaves open relevance to human hypertensive arrhythmia risk or remodeling.
Hypertension-induced cardiac hypertrophy is associated with alterations in ventricular action potentials. To understand molecular mechanisms underlying this electrical abnormality, expression of cardiac voltage-gated K+ channel subunit genes was examined in ventricles of renovascular hypertensive rats. While generating a rat Kv4.3 probe, we discovered a previously unreported 19-amino acid insertion in the C-terminal intracellular region of the channel subunit. RNase protection assays indicated that this novel isoform is predominant in rat lung and heart. Effects of renovascular hypertension were then determined by using renal artery clipping models: two-kidney, one clip (2K-1C) rats, a model of high-renin hypertension with a normal plasma volume, and one-kidney, one clip (1K-1C) rats, a model of normal renin with a raised plasma volume. Expression of Kv4.2 and Kv4.3 mRNAs was diminished by > 50% in ventricles of 2K-1C rats; however, no changes in the expression of Kv1.2, Kv1.4, Kv1.5, Kv2.1, or KvLQT1 mRNAs were detected. Similar downregulation of Kv4.2 and Kv4.3 mRNAs was detected in 1K-1C rats. Chronic administration of captopril, an angiotensin-converting enzyme inhibitor, blocked the development of hypertension and the suppression of Kv4 subfamily channel mRNA expression in 2K-1C rats. Furthermore, captopril administration to sham-operated rats significantly increased Kv4.2 mRNA. These results indicate that renovascular hypertension causes specific reductions in Kv4 subfamily channel mRNA expression and that this effect is likely to be mediated primarily by an increase in cardiac afterload.
No takes yet. Share an insight, caveat, or question.
Takimoto et al. (1997) studied Renovascular hypertension. Renovascular hypertension vs. Sham operation was evaluated on Expression of Kv4.2 and Kv4.3 mRNAs in ventricles (>50% reduction). Renovascular hypertension diminished the expression of Kv4.2 and Kv4.3 mRNAs by >50% in rat ventricles, an effect blocked by chronic captopril administration.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: