Adrenomedullin gene delivery attenuates renal damage and cardiac hypertrophy in Goldblatt hypertensive rats

Adrenomedullin (AM) is a potent vasodilator and natriuretic peptide that pl ays an important role in cardiovascular function. In this study, we employe d a somatic gene delivery approach to explore its potential protective role in renovascular hypertension. A single tail vein injection of adenovirus h arboring the human AM gene significantly blunted a blood pressure increase that lasted for more than 3 wk in two-kidney one-clip (2K1C) hypertensive r ats. The expression of human AM mRNA was detected in the kidney, adrenal gl and, heart, lung, and liver, and immunoreactive human AM was detected in th e plasma and urine of 2K1C rats after human AM gene delivery. A maximal blo od pressure difference of 28 mmHg was observed 10 days after AM gene delive ry, compared with that in rats injected with the control virus carrying the LacZ gene. Human AM gene delivery significantly attenuated increases in th e ratio of left ventricular weight to heart weight, cardiomyocyte diameter, and fibrosis in the heart, as well as glomerular sclerosis, tubular injuri es, and protein casts in the kidney. The beneficial effects of AM gene deli very were accompanied by increased urinary cAMP levels, indicating activati on of AM receptors. These findings provide new insights into the role of AM in renovascular hypertension and may have significance in therapeutic appl ications in cardiovascular diseases.