The cellular ionic basis of hypertension and allied clinical conditions.
Two central concepts of human hypertensive disease remain poorly understood: (1) elevated blood pressure as merely one component of an underlying systemic condition, characterized by multiple defects in diverse tissues (eg, "Syndrome X"), and (2) the heterogeneity of hypertension, in which different and even opposite clinical responses to different dietary and drug therapies are routinely observed among equally hypertensive subjects. To help explain these clinical phenomena, a unifying "ionic hypothesis" is proposed, in which steady-state elevations of cytosolic free calcium and suppressed intracellular free magnesium levels, characteristic features of all hypertension, concomitantly alter the function of many tissues. In blood vessels this causes vasoconstriction, arterial stiffness, and/or hypertension; in the heart, cardiac hypertrophy; in platelets, increased aggregation and thrombosis; in fat and skeletal muscle, insulin resistance; in pancreatic beta cells, other endocrine tissues, and sympathetic neurons, potentiated stimulus-secretion coupling resulting in hyperinsulinemia, increased sympathetic nerve activity, and so on. Furthermore, an analysis of cellular biochemical, dietary-nutrient, and hormonal factors that normally regulate steady-state levels of these intracellular ions suggests an ionic equivalent to Laragh's volume-vasoconstriction analysis of hypertension. This provides a cellular-based explanation for the heterogeneity of hypertension and a rational basis for individualizing dietary and drug recommendations among different hypertensive subjects.
Resnick
L
L
University Vascular Center, Wayne State University Medical Center, Detroit, MI, USA.
D000818:Animals; D001693:Biological Transport, Active; D002118:Calcium / Q000378:metabolism*; D004038:Diet, Reducing; D005947:Glucose / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D050356:Lipid Metabolism; D008274:Magnesium / Q000378:metabolism*; D012083:Renin / Q000378:metabolism; D017673:Sodium Chloride, Dietary / Q000378:metabolism; D015431:Weight Loss
D007328:Insulin; D017673:Sodium Chloride, Dietary; D012083:Renin; D008274:Magnesium; D005947:Glucose; D002118:Calcium