Calcium metabolism in the pathophysiology and treatment of clinical hypertension.
Two parallel lines of research increasingly implicate calcium in the pathophysiology of hypertension. Studies at the molecular-cellular level reveal that, as part of a second messenger system, calcium plays a critical role in cellular responses that are of special relevance to blood pressure homeostasis. Investigations at the epidemiological and clinical levels have also increasingly involved calcium in hypertension, although the data produced are often contradictory, suggesting alternately that hypertension involves excess calcium and that the disorder is associated with a calcium deficiency. In our own research, which emphasizes both the biochemical and the clinical heterogeneity of the hypertensive process, we have found that divalent cation metabolism may be shifted in both directions away from average normotensive values among different types of hypertension. In addition, these calcium metabolic shifts appear to mediate the pressor effects of salt in both human and experimental forms of hypertension and may help identify individuals for whom different therapeutic regimens would be appropriate. We have developed a working cellular hypothesis in which all forms of hypertension are seen as calcium-dependent. One form is more critically dependent on extracellular calcium and is characterized by low plasma renin activity, dietary salt sensitivity, and therapeutic responsiveness to oral calcium supplementation and to calcium-channel blockade. At the opposite extreme, the intracellular calcium-dependent, angiotensin II-mediated form is characterized by high renin, lack of salt sensitivity, and preferential response to beta-blockade and converting-enzyme inhibition.
Resnick
L M
LM
Cardiovascular Center, New York Hospital-Cornell Medical Center, NY 10021.
D000284:Administration, Oral; D002118:Calcium / Q000378:metabolism* / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use; D004032:Diet; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007425:Intracellular Membranes / Q000378:metabolism; D008955:Models, Cardiovascular; D012965:Sodium Chloride / Q000494:pharmacology
D002121:Calcium Channel Blockers; D012965:Sodium Chloride; D002118:Calcium