Development of pharmacological screening method for evaluation of effect of drug on elevated pulse pressure and arterial stiffness.

INTRODUCTION: Elevated pulse pressure (PP) and amplification of arterial stiffness (AS) are responsible for various cardiovascular disease and deaths. Numerous investigations have identified that different antihypertensive agents influence PP and AS differently. None of the previous studies described any reliable animal model particularly to screen drugs having effects on PP and AS. In present study, we developed an animal model to screen such drugs particularly affecting PP and AS.

METHODS: Elevation of PP and amplification of AS were induced in rats by uninephrectomy along with high salt intake (NaCl 4% w/v) for a period of six weeks, and weekly changes in body weight, PP, systolic, diastolic, mean pressure and pulse wave velocity (PWV) were estimated. After six weeks, collagen elastin ratio of aortic segment was estimated. Histomorphometry of abdominal aortic section of rats was done using trinocular microscope.

RESULTS: After six weeks, uninephrectomized rats that were kept on high salt drinking water shown significant increase (P < 0.001) in MAP, PP and PWV indicates that hypertension along with elevated PP developed in rats, and increase in collagen/elastin ratio (P < 0.001) as well as PWV as compared to normal rats indicates the increase in AS.

CONCLUSION: The development of condition of hypertension in conjunction with increase in PP and AS in rats can be used as in-vivo screening model to determine the potency of drugs for the treatment of hypertension or other cardiovascular diseases associated with high PP and AS.