Cardiovascular responses to verapamil and nifedipine in hypoventilated and hyperventilated rats

Abstract

1The influence of hypoventilation or hyperventilation on blood pressure and pulse rate responses to verapamil and nifedipine was studied in chloralose-anaesthetized rats. 2 Artificial ventilation with room air at a fixed volume of 1Oml kg-1 successfully induced combinations of hypoxaemia, hypercarbia and acidosis at a ventilator rate of 37 strokes min-1 and of hyperoxaemia, hypocarbia and alkalosis at 160 strokes min- '. 3 Hypoventilation caused significant decreases in both the blood pressure and pulse rate, whereas hyperventilation produced significant increases in these parameters. 4 In the controls, intravenous injections of graded doses of either verapamil or nifedipine caused dosedependent decreases in mean blood pressure. The effects on pulse rate were not marked. 5 The hypotensive effects of verapamil were significantly more intense in hyperventilated rats, whereas those of nifedipine were significantly less pronounced in hypoventilated animals. The hypoventilated rats exhibited a significant dose-dependent decrease in pulse rate in response to verapamil administration. 6 It is concluded that cardiovascular responses to verapamil, nifedipine and probably other calcium antagonists are altered in the presence of blood gas abnormalities.

Cardiovascular Responses to Nifedipine in Anaesthetized Rats With Abnormal Blood Gas/Ph Levels

“…The absence of acidosis could, at least partly, explain the unaltered responses to nifedipine in the hypoxaemia group, as observed in the current study. Nevertheless, the present findings suggest that the previously observed changes in cardiovascular responses to nifedipine in hypoventilated or hyperventilated rats (Achike & Dai 1990a) were not mainly due to arterial Po2 changes.…”

“…The normal ventilation group was, therefore, used as the control group. The results of the observations on the blood gases/pH in rats subjected to various experimental conditions also give support for the methods by which hypoxaemia, hyperoxaemia, acidosis and alkalosis were induced (Achike & Dai 1990b). The method of creating acidosis and alkalosis is similar to that adopted by previous workers (Eckenhoff et al 1947;Goodyear et al 1961).…”

“…Calcium channel blockers have been shown to ameliorate ischaemic organ damage in several animal models (Kazda et al 1982;Steen et al 1985;Deshpande & Weiloch 1986) and are currently in clinical use for the management of this condition (Selwyn & Braunwald 1987). As blood gas and pH changes often accompany ischaemic organ damage, the possibility that alterations in blood gas/pH levels can affect the cardiovascular responses to verapamil or nifedipine has already been examined and confirmed in a previous study in rats (Achike & Dai 1990a), in which hypoventilation or hyperventilation induced a combination of hypoxaemia, hypercarbia and acidosis or of hyperoxaemia, hypocarbia and alkalosis, respectively. It was, however, not clear which component of blood gases/pH level was the most important determinant of the observed phenomenon.…”

“…It was, however, not clear which component of blood gases/pH level was the most important determinant of the observed phenomenon. A later study showed that changes in blood pH played a more important role than Po2 alterations in affecting the cardiovascular responses to verapamil in the presence of blood gas abnormalities (Achike & Dai 1990b). The present study, therefore, examines the effects of changes in individual blood gas/pH parameters on the cardiovascular responses to nifedipine in rats.…”

EFFECTS OF BLOOD GAS/pH ABNORMALITIES ON THE CARDIOVASCULAR ACTIONS OF VERAPAMIL IN RATS

“…The findings suggest that the arterial pH rather than the PO, changes that accompany hypoventilation or hyperventilation are responsible for the altered cardiovascular responses to verapamil observed in hypoventilated or hyperventilated rats in a previous study (Achike & Dai 1990). …”