COUNTERPOINT: Molecular Analysis of the Angiotensin II Receptor*

I. Introduction THOUGH Tigerstedt described the ability of a kidney extract to influence blood pressure in 1898 (1), it is within this century that the remarkable physiology and medical significance of the renin-angiotensin system has been delineated. Within the last 5 yr, two new developments have taken place, the synthesis of nonpeptidic antagonists of angiotensin II and, most recently, the isolation of complementary DNA encoding the vascular form of the angiotensin II receptor. These two developments are intellectually linked and complementary; they foreshadow future directions in understanding and manipulating the renin-angiotensin system. Here, we describe our research that led to the isolation of cDNA encoding the rat vascular angiotensin II receptor (2). Until the development of nonpeptidic antagonists of angiotensin II, pharmacological studies of angiotensin II receptors employed angiotensin II or other peptide analogs. Such studies demonstrated a heterogeneity of apparent receptors based on pharm...