Effect of chronic nifedipine treatment on blood pressure and adrenergic responses of isolated mesenteric artery in young rats with developing spontaneous hypertension

It is documented that in chronic hypertensive state there is anincreased vasodepressor response to calcium channel antagonistssuch as the dihydropyridine derivate nifedipine. This effect isgenerally proportional to initial blood pressure as wasdemonstrated in several models of experimental hypertension. Inthe present study we investigated the effect of chronic nifedipinetreatment on the development of cardiovascular system in youngspontaneously hypertensive rats (SHR) in order to evaluatewhether it could prevent the abnormalities leading tohypertensive state. Four- and eight-week-old rats were treatedwith nifedipine (50 mg/kg/day) for 4 weeks. Blood pressure ofnifedipine-treated SHR remained at the initial level in contrast totheir untreated controls where it continued to increase. In bothage groups, chronic nifedipine administration reduced neurogeniccontractions of isolated superior mesenteric artery, but did notsignificantly affect the dose-response curve to exogenousnoradrenaline in 8-week-old rats. In contrast, maximum responseto noradrenaline was significantly attenuated in mesenteric arteryof 12-week-old nifedipine-treated SHR. We can presume that theantihypertensive effect of nifedipine is similar in both stages ofspontaneous hypertension development, but the mechanismsinvolved might be different. It seems that chronic reduction ofcalcium influx during the rapid phase of pathological bloodpressure increase in SHR may eliminate the effect of enhancedsympathetic tone, which may have unfavorable consequences oncardiovascular structure and function.