The overall goal of this pilot study is to confirm preliminary data which indicates that papillary muscles isolated from the posterior right ventricular (RV) wall of spontaneously hypertensive (SHR) and spontaneously hypertensive-stroke prone (SHRSP) rats demonstrate an increased sensitivity to a 30 minute hypoxic exposure and subsequent reoxygenation as compared to RV preparations isolated from normotensive Wistar Kyoto (WKY) rats. This hypoxia sensitivity is manifested as significant differences in resting and developed tension, as well as 22Na and 47Ca transport kinetics during both the hypoxic and reoxygenation periods. Experiments will be conducted to test the following hypothesis: Increased hypoxia sensitivity observed in cardiac muscle from SHR and SHRSP is due to an inherent myocardial instability that is not secondary to the development of hypertension. Experiments will be conducted to determine if this increased hypoxia sensitivity: 1) is due to an alteration in the electrical threshold of the preparation or an altered ability of the SR to accumulate and/or release Ca++: 2) develops prior to the development of hypertension or is secondary to the development of hypertension; 3) alleviated by acute increases in [Mg++]omicron during hypoxia and subsequent reoxygenation; 4) alleviated by the addition of pyruvate during hypoxia and subsequent reoxygenation; and 5) alleviated by prior I.P. injection of the membrane stabilizer chlorpromazine.
