Involvement of the Adrenal Glands in the Hypotensive Response to Bromocriptine in Spontaneously Hypertensive Rats

Abstract

1 The dopamine agonist, bromocriptine, produced a hypotensive response following oral administration to conscious normotensive and spontaneously hypertensive (SH-) rats. 2 In SH-rats the dose-related falls in blood pressure to bromocriptine, 3 to 30 mg/kg orally or intraperitoneally, were biphasic, an initial fall at 1 h being followed by some recovery at 2 h and a subsequent fall in blood pressure at 4 and 6 h.3 The dopamine antagonists, metoclopramide, sulpiride, haloperidol and pimozide, had little or no effect on the hypotensive response to bromocriptine, 10 mg/kg orally, in SH-rats. 4 Pretreatment with a-methyl-p-tyrosine augmented the hypotensive response to bromocriptine, 10 mg/kg orally, in SH-rats.5 In adrenal demedullated SH-rats, the hypotensive response to bromocriptine, 3 to 30 mg/kg orally, was abolished.6 In SH-rats the hypotensive response to bromocriptine, 10 mg/kg orally, was prevented by the ,3-adrenoceptor blocking drugs, propranolol and oxprenolol, but was unaffected by (+)-propranolol and by the cardio-selective ,8-adrenoceptor blocking drug, atenolol. 7 In SH-rats pretreated with bromocriptine, 10 mg/kg orally, and then anaesthetized, the pressor responses to low doses of intravenous adrenaline were reversed to depressor, indicating that bromocriptine possesses a-adrenoceptor blocking activity.8 The results suggest that the hypotensive response to bromocriptine in conscious SH-rats is mediated by adrenaline released from the adrenal medullae which, in the presence of a-adrenoceptor blockade, stimulates vascular,f-adrenoceptors producing vasodilatation.

Haemodynamic effects of bromocriptine in the conscious spontaneously hypertensive rat

“…The dose of bromocriptine used (0.3mgkg-1 s.c.) was low in comparison to that in previous studies in SHR. Hamilton (1981) studied the effects of 1-30 mg kg-1 orally administered bromocriptine, whereas Sowers (1981) and Hutchinson et a1 (1981) gave a 1-week i.p. dose of approximately 1.2-2 mg kg-1 day-'.…”

“…A decrease in blood pressure was observed in several species, including man, after the administration of different dopamine receptor stimulants, such as bromocriptine (Lewis 1978;Hamilton 1981 ;Hutchinson et al 1981), lergotrile (Barrett & Lokhandwala 1981), NN-di-n-propyldopamine (Cavero et al 1981;Hahn & MacDonald 1982), and pergolide (Yen et all979;Hahn 1981). The mechanisms underlying the fall have yet to be elucidated.…”

“…A decrease in vascular tone following bromocriptine administration to the conscious spontaneously hypertensive rat (SHR) was proposed, either because of a decrease in circulating vasopressor substances (Hutchinson et al 1981) or P-adrenoceptor mediated vasodilatation following adrenaline release from the adrenal medulla (Hamilton 1981). However, direct haemodynamic measurements to prove such a decrease in vascular tone are so far lacking.…”

Central Bromocriptine‐Induced Tachycardia is Reversed to Bradycardia in Conscious, Deoxycorticosterone Acetate‐Salt Hypertensive Rats

“…Tachycardia elicited by bromocriptine was shown to be elicited by central dopamine D 2 receptor activation, since it was antagonized by intravenous pretreatment with neuroleptics able to cross the blood-brain barrier and was also inhibited by domperidone given into a lateral cerebral ventricle . Because it is also completely abolished by pretreatment with intravenous propranolol (Lahlou & Demenge 1991), the tachycardia may be mediated by b-adrenoceptors stimulated by bromocriptine-induced epinephrine release from adrenal medulla (Hamilton 1981). However, bromocriptine-induced tachycardia was unaffected by adrenalectomy .…”

Hemodynamic Effects of Two Ergot Derivatives in the Conscious Spontaneously Hypertensive Rat

“…Thus, although a vasopressor effect is one of the main classical properties of ergot alkoloids, several derivatives synthesized in the past few years have been shown to lower blood pressure in both normotensive and hyperten sive humans and animals [2][3][4][5][6]. The mecha nism of this hypotensive effect is still not fully explained, and may involve several properties of ergot derivatives including cen tral and/or peripheral dopaminergic action [7][8][9], blockade of postsynaptic a preceptors [10] and stimulation of presynaptic cb-receptors [2],…”