Transplant drug a clue to hypertension?

Transplant drug a clue to hypertension?

By studying kidney transplant patients, scientists at the University of Alabama at Birmingham hope to understand essential hypertension, which is high blood pressure of unknown cause. Most of the estimated 60 million U.S. cases of high blood pressure fit into this category, which carries a higher risk of heart, kidney and blood vessel disease. An explanation of why the drug cyclosporine can increase blood pressure should give information on the basic biological mechanisms involved in developing hypertension.

Since it received federal approval in 1983, cyclosporine has significantly improved transplant survival through its suppression of the immune system. Clinicians, however, have noted an increased incidence of high blood pressure in cyclosporine-treated animals and humans. For example, among cardiac transplant patients on the drug, the incidence of hypertension rises from about 10 percent to 90 percent or more. In high doses it is known to be toxic to the kidneys, which are thought to help maintain blood pressure and salt levels. To piece together the picture of hypertension, John L. Curtis and his co-workers in Birmingham have been studying patients receiving transplanted kidneys and various immunosuppressive drugs, including cyclosporine.

Although the 25,000 kidney transplants done annually in the United States could account for only a small percentage of people with hypertension, Curtis said last week that kidney transplant patients treated with cyclosporine may serve as models of high blood pressure.

By giving kidney recipients fluctuating amounts of salt, Curtis has been able to measure changes in blood flow and pressure in their kidneys. When comparing cyclosporine-treated patients with those not receiving the drug, says Curtis, "it is clear that [cyclosporine] does have acute [blood flow] effects, most of which are reversible." In describing this new form of drug-induced hypertension, Curtis says it is "compressed in time," quickly appearing and disappearing with drug administration and withdrawal. When 14 patients stopped taking cyclosporine, their renal vascular resistance (a measure of pressure in the kidneys related to blood vessel size) dropped by about 36 percent, says Curtis. Because these results suggest that lowering the dose might alleviate the hypertension problem, he is currently testing the effects on blood pressure of different doses of cyclosporine.