Increased Atrial Natriuretic Factor Receptor Density in Cultured Vascular Smooth Muscle Cells of the Spontaneously Hypertensive Rat: Revised

Abstract

To explore the role of the atrial natriuretic factor (ANF) system in the pathophysiology of hypertension we examined the binding kinetics of synthetic ANF to cultured vascular smooth muscle cells (VSMCs) derived from the spontaneously hypertensive rat (SHR) and two normotensive controls-the Wistar Kyoto (WKY) and American Wistar (W). The number of maximal binding sites (Bmax) per cell (mean ± SEM; × 10³) were: SHR = 278.0 ± 33.0, WKY = 28.3 ± 7.1 and W = 26.6 ± 4.2. The differences between the SHR and normotensive strains were significant at p<0.001. The equilibrium dissociation constant (Kd; × 10⁻⁹M) was higher in SHR VSMCs (0.94 ± 0.14) than in WKY (0.22 ± 0.09; p <0.01) and W (0.39 ± 0.14; p <0.02) cells. The plasma levels of the imnunoreactive ANF were higher in SHR than the normotensive controls. We suggest that the relatively greater ANF receptor density in cultured VSMCs of the SHR represents a response to the invitro environment which is relatively more deficient in ANF for VSMCs of the SHR as compared with the normotensive rats. Thus, the capacity of the SHR VSMC to regulate ANF receptor density appears to be independent of the blood pressure level.

Key Words:

• Atrial natriuretic factor
• Receptor density
• Cultured vascular smooth muscle cells
• Spontaneously hypertensive rat