Action of Diazoxide

The Kidney and Hypertension SIR,-The conclusion of your leading article on " The Kidney and Hypertension" (August 25, p. 530) was that there is an increased sensitivity of the vessel wall to the normal activity of the sympathetic system. This increase in sensitivity may be due to a combination of chemical and mechanical changes. Burn and Rand1-4 have shown that a pressor substance resembling noradrenaline is present in the walls of large vessels, and disappears after sympathectomy or repeated injections of reserpine. There is an increased response to noradrenaline in perfused hind limbs of animals treated with reserpine, and this response returns to normal after infusion of noradrenaline. In 1957 it occurred to me that the increased sensitivity of vessels in the chronic phase of renal hypertension may be partly due to disappearance of noradrenaline from the walls. Preliminary observations were encouraging, but I have not had the opportunity to repeat them. The pressor activity of saline extracts of rabbit aorta was assayed in rats which were either pithed or anaesthetized with urethane, with ganglion block by hexamethonium. The pressor activity of extracts of twelve control aortas was equivalent to between three and seven (mean 5.5) gamma noradrenaline/gramme aorta. Hypertension was induced in rabbits by constricting the abdominal aorta above the renal arteries with a silk ligature. In one rabbit where the bloodpressure, measured by ear capsule, had risen from 85 to over 180 mm. Hg in one month, the pressor effect of the aortic extract was within normal limits (Fig. 1). Two rabbits with blood-pressures of 120 to 160 mm. Hg were killed after six months and the aortic extract assayed in five rats. The blood-pressure response was quite unlike that of the control extracts (Fig. 2). It did not resemble adrenaline, noradrenaline, or histamine. It is tempting to suggest that noradrenaline had disappeared from the vessel wall.