Abstract :
Increased sympathetic activity is clearly present in about 30% of patients with mild hypertension. As hypertension advances the sympathetic stimulation has different effects on the heart versus blood vessels; at the level of the heart, beta-adrenergic receptors down regulate and responsiveness decreases, whereas alpha-adrenergic vascular responsiveness increases. The mechanism of increased alpha-adrenergic responsiveness is related to structural changes in the vascular wall - the hypertrophy of the medial layer in the resistance vessel amplifies vasoconstriction to all constrictive agonists. There is evidence that vascular and cardiac hypertrophy in hypertension is more likely to occur in patients with increased sympathetic tone (due to alpha-adrenergic trophic mechanisms).
The enhanced alpha-adrenergic vasoconstriction has two consequences: a) it causes acceleration of hypertension, and b) it may be responsible for insulin resistance. Our data strongly suggest that alpha-adrenergic vasoconstriction causes a functional bypass in the microcirculation of the skeletal muscles, nutritional blood flow to muscle cells decreases and because of that the insulin-stimulated extraction of glucose decreases. In clinical practice alpha1-adrenergic blockade substantially decreases insulin resistance. Since insulin resistance and its consequences - high plasma insulin level - leads to dyslipidemia and injury of the vascular wall, better treatment of hypertension with agents that control the blood pressure and at the same time improve insulin sensitivity may further improve the efficacy of anti-hypertensive treatment in decreasing of coronary heart disease.
Prospective trials will show whether this well-reasoned expectation of a better anti-coronary profile of vasodilators translates into better clinical practice.
