Carbon monoxide is endogenously formed as an end-product that from the biological degradation of heme, via enzymatic degradation by heme oxygenase. While once regarded only as a stable waste product, there since has been considerable evidence amassed which implicates cardiovascular roles for endogenously- derived carbon monoxide. This project will ascertain the acute and chronic hemodynamic consequences of enhanced and impaired production of endogenously formed carbon monoxide using hypertensive and normotensive rat models. Endogenously formed carbon monoxide will be increased by application heme-L-lysinate which provides heme substrate for heme oxygenase-mediated formation of carbon monoxide. Conversely, this formation of carbon monoxide will be inhibited by non-metabolizable heme analogues, such as chromium mesoporphyrin. Tissue levels of carbon monoxide content will be determined by gas chromatography and tissue microsomal heme oxygenase activity will also be determined by metabolic assay. Hemodynamic and renal functional parameters will be measured before and after enhancement and inhibition of heme oxygenase-mediated formation of carbon monoxide in intact animals, and the vasoactive properties of these maneuvers will also be determined in isolated preparations of heart, kidney, and resistance vessels. These studies provide information on the hemodynamic contributions of endogenously- formed carbon monoxide, under normotensive and hypertensive conditions; these studies will establish if aberrations on porphyrin metabolism may contribute to, or conversely, impact on hypertension. As hemolysis and heavy metal poisoning may alter heme oxygenase activity via provision of heme substrate or via endogenous formation of non-metabolizable heme analogues, respectively, these studies may ultimately provide important information related to the on the potential cardiovascular health consequences that often accompany shock and heavy metal poisoning.