Chronic Effects of Diltiazem on the Hemodynamic and Sympathoadrenal Tone in Responsive and Nonresponsive Hypertensive Patients at Rest and During Isometric Exercise

The objective of this study was to identify hemodynamic and sympathetic parameters that could be predictive of the hypotensive response to diltiazem (DTZ). Parameters of cardiovascular functions were measured from M-mode echocardiography and the index of sympathoadrenal tone was given by circulating catecholamine levels in 25 normotensive subjects and in 19 mild-to-moderate hypertensive patients before and after 2 months as well as 12 months (responders only) of treatment with DTZ (SR 120 or 180 mg b.i.d.). The responder (R) subgroup (63% of total population) consisted of patients who showed a decrease in mean arterial pressure (MAP) ≥5 mm Hg (day average) by ambulatory blood pressure (BP) monitoring. Before treatment, R patients were characterized by higher circulating norepinephrine (NE) levels and by hyperkinetic cardiac functions [increased heart rate (HR). cardiac index (CI), and mean velocity of circumferential fiber shortening, p < 0.05] while peripheral resistance was normal. In contrast, non-responders (NR) were characterized by higher peripheral resistance p < 0.05) and normal cardiac functions. Following treatment, hyperkinetic cardiac functions were normalized but the peripheral resistance was unchanged in the R subgroup whereas in the NR subgroup, cardiac parameters were slightly increased and the peripheral resistance was normalized. During isometric exercise, cardiac performance was found to be impaired p < 0.05) and the increase in peripheral resistance was greater (p < 0.05) in the R subgroup before treatment, whereas those responses were normal in the NR group. Treatment with DTZ attenuated the peripheral resistance response and improved cardiac performance in the R subgroup, whereas in the NR subgroup those responses were cither unchanged or worsened following treatment. In conclusion, it thus appears that hyperkinetic cardiac function is a better predictor than increased peripheral resistance of the hypotensive response to DTZ treatment.