Use of a biological peptide pump to study chronic peptide hormone action in transgenic mice - Direct and indirect effects of angiotensin II on the heart

Angiotensin II is a peptide hormone regulator of blood pressure and fluid b alance in mammals. Evidence obtained largely in vitro has also suggested th at angiotensin II has growth-promoting effects and that it might thereby co ntribute to such pathological phenomena as cardiac hypertrophy, a major ris k factor for cardiovascular mortality. It has been difficult to test for th e direct growth-promoting effects of angiotensin II in vivo, however, becau se of the generalized effects of the peptide on hemodynamics. To overcome t his limitation and to test for cardiac-specific functions of angiotensin II , we generated transgenic mice expressing an angiotensin II-producing fusio n protein exclusively in cardiac myocytes. Our findings are the first to di stinguish between local and systemic effects of angiotensin II on the heart and introduce a novel technique for studying tissue-specific peptide funct ion.