Possible participation of angiotensin II receptor subtype 1 in development of hypertension

Angiotensin II (Ang II) is one of the major important factors operating in the pressor system in the regulation of blood pressure. Many investigators have suggested that locally generated Ang II plays an important role in this system. Thus, we examined the change in the expression of Ang II receptors, particularly subtype 1 (AT1), in response to Ang II in isolated aortic strips during development of hypertension in spontaneously hypertensive rats (SHR) in comparison with that in Wistar Kyoto rats (WKY). A radioligand receptor binding assay was used to determine the number of Ang II receptors and to characterize the percentages of AT1 receptors in the aorta at three developmental ages: 3, 6, and 30 weeks. The number of Ang II receptors (Bmax) in the SHR was similar to that in WKY and decreased with age in both SHR and WKY. However, the number of AT1 receptors was higher (57.1, 45.5 and 42.0 fmol/mg protein, respectively) in SHR than in the WKY (33.4, 23.7, and 25.8 fmol/mg protein) at the three ages examined. The pD2 value for Ang II-induced contractions was 9.35 in SHR and 8.85 in WKY at 3 weeks of age. In addition, the maximum developed tension in the aorta of SHR (30.2 mg/mg tissue) was significantly higher than that in WKY (21.8 mg/mg tissue). These findings suggest that the vascular renin-angiotensin system, at a young age before the development of high blood pressure, is activated and participates in the development of hypertension in SHR.