The role of arterial mineralocorticoid receptors in the mechanism of hypertension: findings and hypothesis.
Alterations in electrolyte transport across cell membrane of vascular smooth muscle (VSM) and changes in hemodynamics [increased extracellular fluid volume (ECFV) and cardiac output (C.O.)] have been implicated in the pathogenetic mechanisms of both mineralocorticoid-induced hypertension (MH) and essential hypertension (EH). We have previously found that mineralocorticoids (MC) can act directly on arterial wall by means of a receptor-mediated mechanism, and have postulated that this mechanism is of critical importance in the increased reactivity of VSM to vasoconstrictive stimuli in MH. We now present evidence that a MC-antagonist at the MC-receptor level, progesterone, prevents induction of changes in VSM cell-membrane permeability to Na+ by MC, and development of hypertension. This study has been carried out on rabbits made hypertensive by s.c. implantation of silastic rubber strips impregnated with 11-desoxycorticosterone (the inducer) and/or 50 times that amount of progesterone (the anti-inducer). We hypothesize that the VSM cell-membrane defect (MC-induced in MH and congenital in EH) initiates two separate sequences of biochemical events. One leads, in early stages of hypertension, to expansion of ECFV, increase in C.O., myogenic vasoconstriction and hypertension. When kidney function matures, hypertension recedes. The second sequence of events leads to hypertension via an increase in [Na]i of VSM, leading to an increase in [Ca]i, and an increased contractility of VSM. This hypertension persists. The two sequences are concomitant but independent of each other.
D000818:Animals; D001158:Arteries / Q000378:metabolism*; D002463:Cell Membrane Permeability; D003900:Desoxycorticosterone / Q000097:blood; D006706:Homeostasis; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000097:blood; D011374:Progesterone / Q000097:blood; D011817:Rabbits; D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid / Q000502:physiology*; D012964:Sodium / Q000097:blood; D014661:Vasoconstriction
D018161:Receptors, Mineralocorticoid; D011987:Receptors, Steroid; D003900:Desoxycorticosterone; D011374:Progesterone; D012964:Sodium; D011188:Potassium