Cytosolic Ca2+, Na+/H+ antiport, protein kinase C trio in essential hypertension.
The relationships among the cytosolic free Ca2+ (Cai), protein kinase C (PKC), and the Na+/H+ antiport may hold the key to unraveling the causes and origin of essential hypertension. Increased cellular Ca2+, accelerated Cai turnover rate, or both occur in concert with activation of PKC and the Na+/H+ antiport in a variety of cells. In the vascular smooth muscle cell a rise in Cai produces increased tone and in the kidney it enhances sodium retention through stimulation of the Na+/H+ antiport in the renal tubules. In skeletal muscle increased Cai and augmented PKC activity produces insulin resistance, which is a major characteristic of essential hypertension. Moreover, elevation of Cai, in conjunction with increased activities of PKC and the Na+/H+ antiport, may exert trophic effects on the vasculature and the heart, thereby explaining the narrowing of the vascular lumen in peripheral arteries and the cardiac hypertrophy of long-standing hypertension. Because essential hypertension is a common disorder, its evolutionary advantage in primeval times could rest in skeletal muscle, where higher Ca2+ stores and increased Na+/H+ antiport activity enhanced muscular performance and provided a crucial survival element.
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Hypertension Research Center, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D003600:Cytosol / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
D017923:Sodium-Hydrogen Exchangers; D011493:Protein Kinase C; D002118:Calcium