Increased peripheral resistance is the hallmark of hypertension. It may result in part from exaggerated vascular reactivity of resistance arteries. Some changes in density of surface receptors for different vasoconstrictors and vasorelaxants have been described that could play a role in physiological findings in hypertension. Smooth muscle cells of resistance arteries have increased cytosolic free calcium concentration in some models of experimental hypertension, which may contribute to enhance vascular responses. Exaggerated response of the inositol phosphate – calcium pathway has been demonstrated after stimulation with some vasoconstrictor agents such as norepinephrine, angiotensin II, and vasopressin. In contrast, responses to the potent vasoconstrictor peptide endothelin-1 are either normal (in spontaneously hypertensive rats) or blunted (in deoxycorticosterone-salt hypertension). In the latter case, endothelin receptor density, inositol phosphate and diacylglycerol generation, and cytosolic calcium responses agree with blunted response of blood vessels. Increased basal cytosolic calcium and exaggerated sensitivity of myosin light chain to calcium may be mechanisms underlying increases in sensitivity of signal transduction in smooth muscle in some models of hypertension. However, in general, signal transduction of receptors for vasoconstrictors appears to be blunted rather than exaggerated, except for responses to angiotensin II. Altered structure of resistance arteries (remodeling) may be a mechanism that, even in presence of blunted intracellular signal transduction, may result in enhanced pressor responsiveness of blood vessels in hypertension.Key words: second messengers, phospholipases, inositol phosphates, calcium, magnesium, Na+–H+ exchange, protein kinases, cyclic nucleotides, vascular reactivity.
Pathogenetic mechanisms of the hyperresponsiveness of airway smooth muscle in bronchial asthma. - Changes in intracellular signal transduction