As we have shown in these mice, cardiac hypertrophy arises independently of ventricular KATP activity, as a secondary consequence of enhanced vascular KATP activity, resulting in vasodilation; reduced vascular resistance; and, in response, enhancement of renin-angiotensin signaling, adrenergic signaling, or other vasoresponsive pathways (26, 38). This evidence concerns the gene REN and cardiac hypertrophy.