ergoline and Hypertension--Renal

Cardiovascular effects of the dopamine receptor agonists, bromocriptine and lergotrile, were examined in renal hypertensive rats (RHR), spontaneously hypertensive rats (SHR) and in normotensive rats (NTR). In SHR, bromocriptine at 0.3 and 1.0 mg/kg i.p. and lergotrile at 0.3 mg/kg i.p. produced significant decreases in blood pressure and heart rate and the effects were prevented by haloperidol pretreatment. These results are consistent with the hypothesis that bromocriptine- and lergotrile-induced cardiovascular effects are due to a reduction in sympathetic tone via activation of neuronal dopamine receptors. In contrast to SHR, bromocriptine as well as lergotrile, at doses of 0.3 mg/kg i.p., were ineffective in RHR. Only at the 1 mg/kg i.p. dose, both the agents reduced blood pressure in RHR, but increased heart rate and only the effects of bromocriptine were antagonized by haloperidol. The magnitude and the duration of the hypotensive effect produced by both the agents were smaller in RHR than in SHR. The ganglion blocking agent, chlorisondamine, reduced blood pressure equally in RHR and SHR, but not in NTR, indicating a role for the sympathetic nervous system in the maintenance of high blood pressure in both SHR and RHR. It is further suggested that neuronal dopamine receptors that mediate reduction in resting sympathetic tone are less sensitive in RHR as compared to SHR.

Topics: Animals; Blood Pressure; Bromocriptine; Ergolines; Heart Rate; Hypertension; Hypertension, Renal; Male; Rats; Rats, Inbred Strains

The effects on blood pressure and heart rate of a new ergoline derivative, 2(R,S)-Cyano-3-(6-methylergolin-8 beta-yl)-propionamide (355/1057), were evaluated in different models of experimental hypertension as well as in normotensive rats, dogs and cats. Its interference with sympathetic neurotransmission was also studied in anaesthetized cats and dogs and in pithed rats. Dose-related hypotensive effects were found after single oral, intraduodenal and intravenous administration. In all the studied experimental models 355/1057 showed a prompt onset of action and a prolonged effect on blood pressure at low doses without substantially modifying heart rate. Some comparative results obtained with other commercially available antihypertensive agents are also reported. One month daily oral administration in SH-rats produced an antihypertensive effect persisting trough the entire experiment with no signs of tachyphylaxis. In anaesthetized dogs 355/1057 inhibited sthe pressor response elicited by bilateral carotid occlusion and in anaesthetized cats it reduced the response of the nictitating membrane elicited by electrical stimulation of both the pre- and post-ganglionic fibers but not by norepinephrine bolus injection.

Topics: Anesthesia; Animals; Antihypertensive Agents; Blood Pressure; Cats; Dogs; Ergolines; Heart Rate; Hemodynamics; Hypertension; Hypertension, Renal; Male; Rats; Rats, Inbred Strains; Species Specificity