This project will continue the investigator's study of the role of histamine receptors H1 and H2 on blood pressure and permeability of the blood brain barrier (BBB) in normotensive and spontaneously hypertensive rats. To further evaluate the histamine-induced decreases in blood pressure and BBB permeability, the investigator proposes to use a more potent H2 receptor agonist, impromidine, and a different antagonist, ranitidine. He will also study the influence of leukotrienes, another class of autacoid substances involved in the allergic response and in cardiovascular function, in both rat experimental models. Pentobarbital anesthetized rats will receive the agonist and antagonist drugs to be tested via the cannulated jugular vein and their man arterial blood pressures will be recorded via the cannulated femoral artery. Permeability of the BBB will be evaluated by measuring levels of injected radioactive tracers Technetium (99m Tc-sodium pertechnetate) and 1311- radioiodinated serum albumin in cardiac blood and excised brain tissue washed in saline. Of these two markers, the former is a small, actively transported molecule while the latter is a large molecule normally incapable of penetrating the capillary wall. The samples will be counted for gamma emissions and the brain:blood ratio of radioactivity will be calculated. Significant differences among the ratios obtained with different drugs and drug doses in the two strains of rats to be used, will be determined statistically.
