ACUTE AND CHRONIC CALCIUM-ANTAGONIST TREATMENT ELEVATES SYMPATHETIC ACTIVITY IN PRIMARY HYPERTENSION

Eleven men with mild to moderate primary hypertension were studied at rest and during mental stress before and during intravenous infusion o f the calcium antagonist felodipine. Eight of them were restudied duri ng long-term treatment (extended-release felodipine, 10 mg daily). For comparison, 10 normotensive control subjects were studied with the sh ort-term protocol. Heart rate, cardiac output, central cardiovascular pressures, and forearm blood flow were registered. Arterial and venous sampling was performed. Norepinephrine spillovers to arterial plasma and from the forearm were assessed with the use of radiotracer methodo logy. In the hypertensive patients, felodipine lowered mean arterial b lood pressure acutely by 8% (P<.01). Systemic vascular resistance decr eased by 22% (P<.001), cardiac output increased by 20% (P<.01), and no repinephrine spillover to arterial plasma increased by 61% (P<.001). F orearm vascular resistance fell by 30% (P<.001), but norepinephrine ov erflow from the forearm increased by 115% (P<.001). These forearm resp onses were not seen in normotensive subjects despite similar systemic responses to felodipine infusion. After 8 weeks of treatment, mean art erial pressure decreased to 15% below baseline (P<.001), cardiac outpu t returned toward pretreatment levels, and systemic vascular resistanc e remained low. Forearm blood flow returned toward basal levels, but f orearm vascular resistance remained lowered. Total body and forearm no repinephrine spillover values were as elevated as in the acute situati on. The hemodynamic ''defense reaction'' and the sympathoadrenal respo nse to mental stress were essentially unaffected by felodipine. Stress -induced small elevations of neuropeptide Y-like immunoreactivity pers isted during felodipine. Thus, the vasodilatation induced by felodipin e elicits sympathetic counterregulation, which persists in the long te rm with respect to peripheral and total sympathetic activities, despit e resetting of the baroreflex control of heart rate.