A positive and reversible relationship between adrenergic nerves and alpha-1A adrenoceptors in rat arteries.
We evaluated the relationship between the presence of adrenergic nerves and the presence of alpha-1 adrenoceptors (alpha-1 AR) in the arterial tree of the rat. The thoracic aorta and the carotid, mammary, renal and femoral arteries were isolated from 20-week-old male WKY rats, along with the superior mesenteric artery and small (first order) and resistance-sized (third order) side branches of this vessel. Norepinephrine content ([NE]) and specific binding of 300 pM [3H]prazosin were determined. To estimate the total density of alpha-1 AR ([alpha-1 AR]) as well as the density of alpha-1A AR ([alpha-1A AR]), binding experiments were performed with and without pretreatment of the preparations with the irreversible alpha-1B AR and alpha-1D AR antagonist chloroethylclonidine and in the absence and presence of the alpha-1A AR selective ligand (+)-niguldipine (30 nM). Also the presence of mRNA for alpha-1A AR was evaluated by use of reverse transcriptase-polymerase chain reaction (RT-PCR). In intact rats, arterial [NE] ranged between 0.1 and 15 ng/microgram DNA, arterial [alpha-1 AR] ranged between 12.4 and 46.8 fmol/mg protein and [alpha-1A AR] ranged between 0.05 and 27.9 fmol/mg protein. There was no significant correlation between [alpha-1 AR] and [NE]. However, with respect to the [alpha-1A AR] a significant correlation between [NE] and [alpha-1A AR] was observed. RT-PCR analysis confirmed the expression of alpha-1A AR in the densely innervated mesenteric resistance-sized arteries. Two weeks after chemical sympathectomy of the rats with 6-hydroxydopamine (i) arterial [NE] was markedly reduced, and (ii) a distinct reduction in the [alpha-1A AR] as percentage of the total [alpha-1 AR] density in mesenteric artery side branches was noted. These findings indicate that there is a positive and reversible relationship between the presence of adrenergic nerves and that of alpha-1A AR in rat arteries.
Stassen
F R
FR
Department of Pharmacology, Universiteit Maastricht, The Netherlands.
Maas
R G
RG
Schiffers
P M
PM
Janssen
G M
GM
De Mey
J G
JG
D000818:Animals; D001158:Arteries / Q000294:innervation*; D008297:Male; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D018340:Receptors, Adrenergic, alpha-1 / Q000032:analysis*; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000502:physiology*
D018340:Receptors, Adrenergic, alpha-1; D011224:Prazosin