The roles of cell Ca2+, protein kinase C and the Na(+)-H+ antiport in the development of hypertension and insulin resistance.
There is evidence that the cytosolic free Ca2+, protein kinase C, and the Na(+)-H+ antiport cross-communicate with one another through positive and negative feedback mechanisms, thereby maintaining cellular Ca2+ and pH homeostasis. This triumvirate may play a role in the development of insulin resistance--a common characteristic of both essential hypertension and non-insulin-dependent diabetes mellitus. Circulating cells from patients with essential hypertension and non-insulin-dependent diabetes mellitus demonstrate elevated cytosolic free Ca2+, increased protein kinase C activity, or both, and these perturbations are associated with augmented activity of the Na(+)-H+ antiport. If present in other cells (e.g., striated muscle cells and adipocytes), these alterations could underlie insulin resistance in essential hypertension and non-insulin-dependent diabetes mellitus.
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Hypertension Research Center, University of Medicine and Dentistry of New Jersey-N.J. Medical School, Newark 07103-2714.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D003327:Coronary Disease / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000503:physiopathology*; D004285:Dogs; D015536:Down-Regulation; D005246:Feedback; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000150:complications / Q000453:epidemiology / Q000208:ethnology / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D009318:Natriuresis / Q000187:drug effects; D009765:Obesity / Q000150:complications / Q000208:ethnology / Q000503:physiopathology; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D011972:Receptor, Insulin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017923:Sodium-Hydrogen Exchangers; D013564:Sympathetic Nervous System / Q000503:physiopathology
D002352:Carrier Proteins; D007328:Insulin; D017923:Sodium-Hydrogen Exchangers; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D011493:Protein Kinase C; D005947:Glucose; D002118:Calcium