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The myogenic response of blood vessels is an intrinsic response of the smooth muscle to pressure induced stretch causing vasoconstriction to maintain constant blood flow, particularly in critical vascular beds such as the kidney and brain, in the face of changing blood pressure. Additionally, the myogenic response protects these organs from acute elevation of blood pressure. To study this response Fawn-hooded hypertensive (FHH) rats, which do not have a myogenic response, and congenic strains developed in Dr. Roman’s laboratory that have a restored myogenic response, are being studied to determine the specific genetic elements involved in this difference. The role of ion channel function in the myogenic responses of vascular smooth muscle is being examined at the tissue and cellular level. In order to study tissue level responses, middle cerebral arteries are cannulated and pressurized in a chamber permitting video-based measurement of blood vessel diameter changes in response to varying perfusion pressures and/or the application of drugs. Ion channel function is studied using patch clamp methodology on isolated vascular smooth muscle cells. Briefly, the patch clamp technique involves the formation of a high resistance seal between a small-tipped (1㎛) glass pipet with a smooth muscle cell. This permits the measurement of single channel or whole-cell currents. A second project involves measurement of the effects of antifungal drugs on the isolated spontaneously beating rat heart using the method of Langendroff. This project is done in collaboration with Dr John Cleary of the School of Pharmacy. Antifungal agents have known cardiotoxic effects, but the reasons for this toxicity are unknown. The beating hearts are perfused via the coronaries with various drugs while recording the contractile and electrical properties of the heart. The goal is to understand the mechanism of toxicity as well as develop therapeutic strategies for the safe use of these compounds. A third project in collaboration with Dr Jun Ming Wang of Pathology examines a potential therapy for Parkinson’s disease using neurosteroids to stimulate endogenous stem cell expansion and neurogenesis of new dopamine neurons in the nigrostriatum. Parkinson’s disease occurs due to progressive degeneration of dopamine neurons in the nigrostriatum causing tremor and disorders in balance and coordinated movement.
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