Ž . European Journal of Pharmacology 335 1997 193–198 Cardiovascular effects of elgodipine and nifedipine compared in anaesthetized rats Jose M. Valdivielso a , Juan F. Macıas b , Jose M. Lopez-Novoa a, ) ´ ´ ´ ´ a Instituto Reina Sofıa de InÕestigacion Nefrologica, Departamento de Fisiologıa y Farmacologıa, Facultad de Medicina, UniÕersidad de Salamanca, ´ ´ ´ ´ ´ Salamanca, Spain b SerÕicio de Nefrologıa del Hospital UniÕersitario de Salamanca, Salamanca, Spain ´ Received 7 May 1997; revised 24 July 1997; accepted 29 July 1997 Abstract The cardiovascular effects of elgodipine were studied and compared with those of nifedipine in the presence or absence of ganglion Ž . Ž . blockade. A bolus of elgodipine 5–25 mgrkg or nifedipine 60–120 mgrkg was given and sequential cardiovascular effects in rats were recorded. Both dihydropyridines induced a dose-dependent decrease in mean arterial pressure but, whereas nifedipine induced reflex tachycardia, elgodipine induced a dose-dependent bradycardia. Both substances induced decreases in left ventricular d Prd t without max significant changes in central venous pressure. Good linear correlation was observed between the elgodipine-induced decrease in mean arterial pressure and those of heart rate and left ventricular d Prd t . The profile of the decrease in mean arterial pressure in animals max Ž . pretreated with hexametonium chloride 20 mgrkg was the same but the nifedipine-induced tachycardia was abolished without changes in elgodipine-induced bradycardia. These characteristics of elgodipine makes this dihydropyridine a potentially beneficial therapeutic agent in the case of severe hypertension accompanied by obstructive coronopathy. q 1997 Elsevier Science B.V. Keywords: Elgodipine; Blood pressure; Tachycardia, reflex; Dihydropyridin 1. Introduction The effectiveness of the first generation Ca 2q channel Ž . antagonists nifedipine, verapamil and diltiazem in the treatment of a large number of cardiovascular disorders has led to the development of a new generation of Ca 2q entry blockers, with more selective properties. Several reviews have appeared which comment that dihydropy- ridines must be used with caution in patients with coronary heart disease because of the increased mortality observed Ž in patients treated with these drugs Furberg et al., 1995, . 1996; Psaty et al., 1995; Poole-Wilson, 1996 . One of the most discussed undesirable effects to which some authors attribute the mortality is the reflex tachycardia produced Ž by dihydropyridines specially those of the first genera- .Ž . tion Bala Subramanian et al., 1982 . Elgodipine is a recent example of the dihydropyridine 2q Ž structural family of Ca channel antagonists Tamargo et . al., 1991 which has potent coronary dilator properties in ) Ž . Ž . Corresponding author. Tel.: 34-23 294-472; Fax: 34-23 294-669; e-mail: jmlnovoa@gugu.usal.es the anaesthetized pig without significant depression of Ž . cardiac contractility Sassen et al., 1990 . Also, elgodipine does not show a tachycardiac effect in dogs and pigs Ž . Sassen et al., 1990; Drieu la Rochelle et al., 1994 . However, to our knowledge, the effect of elgodipine on cardiac function has not been studied in rats. We have, therefore, designed the present study to com- pare the effects of elgodipine and nifedipine on arterial pressure, heart rate and cardiac contractility in rats in the presence or absence of ganglion blockade. 2. Materials and methods Experiments were carried out in female Wistar rats Ž . weighing about 250 g IFFA-CREDO, France , fed on a standard diet and water ad libitum. All the experiments were performed according to the guidelines for the ethical treatment of the experimentation animals by the European Community and the Spanish Ministerio de Agricultura, Pesca y Alimentacion. ´ The animals were anaesthetized with sodium pento- 0014-2999r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved.