Epinephrine (E) is synthesized in the adrenal by the enzyme phenylethanolamine-N-methyltransferase (PNMT). PNMT is also present in many other tissues along with another N-methyltransferase (NMT) that can also synthesize E. E can raise blood pressure and cause insulin resistance. Both spontaneously hypertensive rats and diabetic rats have elevated tissue levels of PNMT, NMT and E. The rat kidney can synthesize E and excrete that E into urine. Preliminary studies show that hyperinsulinemic human hypertensives have excess urinary E of renal origin. Studies will define how extra-adrenal E synthesis affects plasma and urinary E levels, glucose metabolism and blood pressure control. Rats will have their adrenal medullae removed and be made diabetic. One group will receive SKF7698 to inhibit extra-adrenal E and epinine synthesis. A second group will receive the beta2 adrenergic blocker ICI 118,551. A third group will receive placebo. Animals will be tested for insulin sensitivity to determine if E stimulation of B2 receptors causes insulin resistance. Normal human subjects and hypertensives will undergo 3 H-E infusion and have plasma and urine 3HE and E levels measured to determine plasma E kinetics, urinary E clearance, and to determine the amount of urinary E synthesized by the kidney. Subjects with hyperinsulinemic hypertension will have E levels measured and undergo insulin clamp studies to define the site of insulin resistance at both normal insulin levels and when a normal rate of glucose flux is driven by hyperinsulinemia and hyperglycemia.
Showing the most recent 10 out of 33 publications
