Cytosolic Ca2+ regulation attenuates ANP-induced cGMP response in vascular smooth muscle cells of the SHR.
Cultured vascular smooth muscle cells (VSMCs) of the spontaneously hypertensive rat (SHR) show a higher density (Bmax) of ANP receptors and a blunted cyclic (c) GMP response to the hormone. To explore the idea that a higher cytosolic free Ca2+ (Cai2+) may be responsible for a blunted cGMP response to ANP, we examined the effect of raising Cai2+ by the Ca2+-ionophore A23187 or K+ depolarization on the ANP-induced cGMP response. Treatment of VSMCs from the SHR, Wistar-Kyoto rats (WKY), or American Wistar (WIS) rats with A23187 or high K+ resulted in a uniform reduction of the ANP-cGMP response in 1.8 mmol/L Ca2+ medium but not Ca2+-free medium. We conclude that a higher level of Cai2+, probably at the domain adjacent to the membrane, may inhibit ANP-induced activation of the particulate guanylate cyclase, and that this may be the cause of the blunted cGMP response of SHR VSMCs to ANP.
Nakamura
M
M
Hypertension Research Center, University of Medicine and Dentistry of New Jersey, New Jersey Medical School 07103.
Nakamura
A
A
Hatori
N
N
Fine
B P
BP
Aviv
A
A
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000502:physiology*; D001794:Blood Pressure; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis*; D003600:Cytosol / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D017461:Receptors, Atrial Natriuretic Factor; D011956:Receptors, Cell Surface / Q000502:physiology
D011956:Receptors, Cell Surface; D009320:Atrial Natriuretic Factor; D017461:Receptors, Atrial Natriuretic Factor; D006152:Cyclic GMP; D002118:Calcium