The main objective of this proposal will be to increase dependability of indirect blood pressure measurements for detection of mild hypertension in awake rats. Underlying mechanisms will be explored by first making rats mildly hypertensive (with streptozotocin, sucrose, or high salt diets) and after tail-cuff systolic pressures become appreciably elevated, then intraarterial pressures will be recorded continuously while tail-cuff pressures are being measured. If significant elevations in femoral systolic pressure can be demonstrated, recording of intraarterial pressure will be repeated while the same rats are kept unrestrained in open-topped cages. In other experiments rats will be intentionally subjected to stress by either irregular shaking or heat exposure and ensuing pressor effects will be quantified by both direct and indirect measurements. Additive effects of such stresses on the induction of mild hypertension with streptozotocin, sucrose drinking or dietary salt loading will be compared. If mild hypertension indeed becomes aggravated, then similar experiments will be conducted using DOCA-salt, Dahl salt-sensitive, or spontaneously hypertensive rats to determine whether stress-induced pressor effects also influence tail-cuff detection of established hypertension. Other experiments will test if stress-induced pressor artifacts can be minimized or abolished by pretreating awake rats with diazepam (Valium) prior to tail-cuff measurements. Additionally, development of an alternative method for indirect blood pressure measurements on the hind-leg, instead of the tail, will be explored.
