Experimental Studies on the Effects of Insulin on Central Regulation of Blood Pressure

It has been widely revealed that an insulin-like immunoreactive substance (ILI) is distributed in the brain, particularly in the hypothalamus and circumventricular areas where it is supposed that the balances of water and electrolytes are regulated. Although the insulin synthesis of the brain has not been clarified, the existence of ILI in the brain is clearly demonstrated, and ILI may play some important physiological roles on blood pressure regulation as well as feeding behavior. Taking notice of the Na(+)-K+ ATPase activating action of insulin, we aimed to investigate the central cardiovascular effects of insulin using rats, in comparison with the endogenous digoxin-like immunoreactive substance (DLI), which exists in the same sites of ILI, inhibits Na(+)-K+ ATPase activity, and increases blood pressure. When rats were fed high-salt diets for 4 weeks, hypothalamic and pituitary contents of ILI decreased significantly compared to those of rats on a regular diet. Intracerebroventricular (i.c.v.) infusion of insulin lowered the femoral arterial pressure and decreased the heart rate significantly in both urethane-anesthetized and conscious rats, and inhibited the renal sympathetic activities in urethane-anesthetized rats. Intravenous infusion of the same amounts of insulin, however, influenced neither blood pressure nor heart rate. Simultaneous i.c.v. infusion of insulin abolished the elevation of both blood pressure and heart rate produced by i.c.v. infusion of hypertonic saline. The increase in the plasma DLI was also abolished significantly. Inhibiting central sympathetic nerve activities and DLI secretion from the hypothalamus, cerebral insulin may effect the central regulations of blood pressure, particularly in salt-loading conditions.