Abstract
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 ofalpha-1A AR ([alpha-1A AR]), binding experiments were performed with and without pretreatment of the preparations with the irreversible alpha-1B AR andalpha-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 foralpha-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/μg 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.
Footnotes
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Send reprint requests to: Dr. Jo G. R. De Mey, Ph.D., Dept. of Pharmacology, Universiteit Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
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↵1 This work was supported by grant 902-18-291 PGN of the Netherlands Scientific Research Organization (NWO) and the Netherlands Heart Foundation (NHS) and by the EU-sponsored BIOMED1 initiatives EURAD and EURECA.
- Abbreviations:
- alpha-1 AR
- alpha-1 adrenoceptor
- CEC
- chloroethylclonidine
- NE
- norepinephrine
- KRB
- Krebs-Ringer bicarbonate buffer
- SM α-actin
- smooth muscle α-actin
- RT
- reverse transcriptase
- PCR
- polymerase chain reaction
- bp
- base pairs
- Received February 7, 1997.
- Accepted September 26, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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