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Two forms of vasoconstriction in systemic hypertension
1Cardiovascular Center, New York Hospital-Cornell Medical Center, New York 10021.
Insights
Essential hypertension is not a single condition but a spectrum of diseases. Two distinct vasoconstriction mechanisms, one calcium-related and one renin-related, sustain high blood pressure and offer new therapeutic targets.
Area of Science:
- Cardiovascular Medicine
- Nephrology
- Pharmacology
Background:
- Essential hypertension is traditionally viewed as a singular entity.
- However, clinical and biochemical evidence suggests it is a heterogeneous condition.
- The precise pathophysiological mechanisms underlying essential hypertension remain largely unknown.
Purpose of the Study:
- To characterize essential hypertension as a heterogeneous spectrum of pathophysiologic processes.
- To identify and quantify distinct mechanisms of sustained vasoconstriction in essential hypertension.
- To explore the reciprocal interplay of these mechanisms in maintaining arteriolar tone.
Main Methods:
- Quantification of two distinct vasoconstriction mechanisms in patients with essential hypertension.
- Identification of renin-independent (calcium-related) and renin-mediated (calcium-dependent) pathways.
- Assessment of the influence of sodium balance and plasma renin levels on these mechanisms.
Main Results:
- Two primary mechanisms sustain diastolic hypertension: a renin-independent pathway linked to abnormal calcium transport, and a renin-mediated pathway involving increased cytosolic calcium.
- The renin-independent mechanism is associated with low plasma renin and ionized calcium, correctable by sodium depletion or specific blockade.
- The renin-mediated mechanism is quantifiable by plasma renin levels or response to antirenin drugs.
- These mechanisms interact reciprocally, with one predominating at the extremes of plasma renin levels and both operative in the mid-range.
Conclusions:
- Essential hypertension comprises a spectrum of pathophysiologic processes, not a single entity.
- Understanding these distinct vasoconstriction mechanisms allows for pathophysiological stratification of patients.
- This provides a basis for developing more precisely tailored therapeutic strategies for hypertension.
Abstract:
Clinical, pharmacologic and biochemical evidence characterizes essential hypertension as a heterogeneous spectrum of pathophysiologic substances rather than the single entity it has long been presumed to be. Although the causes of essential hypertension remain obscure, 2 different mechanisms for long-term vasoconstriction that sustain diastolic hypertension in the experimental and clinical forms of primary aldosteronism and renovascular hypertension can also be identified and quantified among patients with essential hypertension. The first mechanism is renin independent, requires antecedent sodium retention and appears related to abnormal membrane transport of calcium. This vasoconstriction is identified by low plasma renin and ionized calcium and is correctable by sodium depletion or calcium channel or alpha blockade. The second vasoconstrictor mechanism is renin mediated and involves an increase in cytosolic calcium. This mechanism is quantifiable by the plasma renin level or the hypotensive response to an antirenin-system drug (converting enzyme inhibitor, beta blocker or saralasin). Depending on the state of sodium balance, these 2 mechanisms contribute reciprocally to maintenance of arteriolar tone in experimental models, in both normal and hypertensive people, and in patients with congestive heart failure. In these situations, at the extremes of the range of plasma renin values, one or the other mechanism predominates, whereas in the medium range of renin values both mechanisms can be operative. These interrelations provide a basis for applying more precisely tailored therapy and for stratifying patients pathophysiologically for further study.