Central norepinephrine pathways are involved in cardiovascular response tointracerebroventricular substance P

AIM: To study the role of norepinephrine system in the cardiovascular respo nse to intracerebroventricular substance P (SP) in rabbit. METHODS: SP was given intracerebroventricularly in anesthetized rabbits pretreated with the catecholaminergic neurotoxin, 6-hydroxydopamine (6-OHDA). The density and affinity of SP receptors on synaptosomal membranes of the hypothalamus and the ventral medulla of rabbits were determined by [I-125]SP receptor assay. Arterial blood pressure and heart rate were recorded. RESULTS: Intracerebr oventricular (icv) pretreatment of rabbits with 6-OHDA, reduced norepinephr ine in the hypothalamus (by 86.7 %) and in the ventral medulla (by 77.0 %) respectively. The presser response and tachycardia of these rabbits to icy SP (3.55 nmol kg(-1)) were attenuated. The density and the affinity of SP r eceptors in the hypothalamus and the ventral medulla of 6-OHDA-lesioned rab bits were decreased. The B-max (pmol g(-1) protein) of SP receptors in hypo thalamus and the ventral medulla are 108 +/- 5, 35.9 +/- 2.2 in control gro up, and 42 +/- 18, 20 +/- 5 in B-OHDA-lesioned rabbits, respectively. K-d ( nmol L-1) of SP receptors in the two regions are 0.015 +/- 0.004, 0.014 +/- 0.006 in control group and 0.029 +/- 0.001, 0.015 +/- 0.003 in 6-OHDA grou p. There is a significant difference of B-max (P < 0.01) and K-d(P < 0.01, P < 0.05) in both regions between 6-OHDA groups and control groups. CONCLUS ION: The suits suggested that central norepinephrine pathways involved in t he cardiovascular response to icy SP.