Increase in the hypotensive effect of bromocriptine induced by spinal transection in rats: contribution of spinal dopamine receptors.
Intravenous (i.v.) administration of bromocriptine (150 micrograms/kg) in conscious normotensive rats with chronic spinal cord transection (at T5-T7), pretreated or not with i.v. propranolol (0.5 mg/kg), induced significant decreases in mean arterial blood pressure (MAP) which were greater and longer lasting than those in intact rats (-15 to -20 as compared with -10 mm Hg) for 8 days after transection. To assess the spinal and/or peripheral origin of this phenomenon, rats were also pretreated with either i.v. (0.3 mg/kg) or intrathecal (i.t.; 93 nmol/rat; at T9-T10) administration of domperidone, a selective dopamine (DA)2 receptor antagonist incapable of crossing the blood-brain barrier (BBB) freely. The increase in hypotension induced by spinal section was suppressed by i.t. but not by i.v. domperidone. In intact rats, bromocriptine elicited an increase in heart rate (HR; approximately 50 beats/min more), which was prevented by i.v. propranolol treatment. In spinal cord-transected rats, however, it had a significant bradycardic effect (approximately 50 beats/min less), which was antagonized by i.t.-administered domperidone. These results suggest that enhancement of the hypotensive effects induced by systemic administration of bromocriptine after a complete thoracic spinal transection is fully mediated by spinal DA2 receptors. This finding may help explain the increased orthostatic hypotension induced by DA receptor agonists in Parkinsonian patients with spinal lesions.
Lahlou
S
S
Laboratoire de Physiologie Pharmacologie II, URA CNRS 1287, Faculté de Pharmacie, Université Joseph Fourier, Grenoble, France.
Demenge
P
P
D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001971:Bromocriptine / Q000008:administration & dosage / Q000494:pharmacology*; D004294:Domperidone / Q000008:administration & dosage / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D007022:Hypotension; D007275:Injections, Intravenous; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000502:physiology*; D013116:Spinal Cord / Q000502:physiology* / Q000601:surgery
D011954:Receptors, Dopamine; D001971:Bromocriptine; D004294:Domperidone; D011433:Propranolol