Membrane transport in vascular smooth muscle and its relation to normal and altered excitation during hypertension.

Evidence is presented for the operation of Cl-Cl exchange diffusional transport system in rat aortic smooth muscle. The efflux of 36Cl associated with this mechanism is doubled in rats made hypertensive with aldosterone-salt treatment. The residual efflux of Cl is similarly elevated in the hypertensives. This finding supports the hypothesis that increased membrane permeability to Cl is associated with aldosterone hypertension. The agonist-induced increases in aortic effluxes of 42K exhibit a 10-fold reduction in the ED50 to norepinephrine in aldosterone hypertensive rats. The possible contributors to this supersensitivity were studied by means of a pharmacologic analysis of the action of competitive (phentolamine) and non-competitive (dibenamine) antagonism of norepinephrine induced increases in 42K efflux. The dissociation constant for phentolamine, KB= 1 x 10-8M, was relatively unaltered in the hypertensive group, as was the dissociation constant for norepinephrine, KA= 3.4 - 5.8 x 10-7M. A substantial increase in receptor number and/or transduction efficiency (3-12 fold) was derived from the analysis. It is tentatively concluded that supersensitivity to norepinephrine during aldosterone hypertension may be more closely related to changes in receptor number and/or efficiency than in receptor affinity.