The hemodynamic profile of the onset of hypertension in the DOCA‐salt rat model

Abstract

The pathogenesis of various forms of experimental hypertension may be mediated by different hemodynamic mechanisms. In the present study we characterized the hemodynamic profile of the onset of hypertension in the DOCA-salt model. Rats were chronically instrumented for measurement of mean arterial pressure (MAP) by telemetry and cardiac output (CO) using a Transonics flow probe on the ascending aorta (N=4). Rats had free access to 0.9% saline and 0.1% NaCl food throughout the protocol. Control data was collected continuously for 7 days before and 10 days following subcutaneous administration of 50 mg of DOCA in a silicone implant. During the 7 day control period, basal values for MAP, CO, heart rate (HR) and total peripheral resistance(TPR) averaged 102 + 1.5 mm Hg, 21 + 1.6 ml/min/100g, 418 + 8.1 beats/min and 5.02 + 0.41 (arbitrary units) respectively. During the first 4 days of DOCA, MAP increased ~8% from baseline in parallel with a ~12% in CO. In contrast heart rate and TPR decreased by ~0.6% and ~8% respectively by Day 4 of DOCA. By Day 10 of DOCA, MAP increased to ~20% above control and CO returned to control levels whereas TPR increased to ~17% above baseline. Heart rate continued to decrease to ~7% below control on Day 10. We conclude that the development of DOCA-salt hypertension is mediated initially by an increase in CO followed by an increase in TPR as the hypertension progresses. Supported by NIH Grant HL 64178.