What is the clinical evidence from this study?

Study design: Other. Population: Vascular wall growth and injury-induced intimal lesion. Intervention: Norepinephrine and alpha-1 adrenoceptor antagonists. Primary outcome: Lumen area, adventitial area, circumference, and neointimal area (p=<0.05).

October 1, 2002

α1-Adrenoceptor stimulation directly induces growth of vascular wall in vivo

Q: What are the key findings of this study?

Perivascular suffusion of norepinephrine directly induced vascular wall growth and augmented injury-induced intimal lesion growth, an effect attenuated by an alpha-1A adrenoceptor antagonist.

Key Result

Perivascular suffusion of norepinephrine directly induced vascular wall growth and augmented injury-induced intimal lesion growth, an effect attenuated by an alpha-1A adrenoceptor antagonist.

Structured PICO

Does norepinephrine directly induce growth of the vascular wall in vivo?

Population

Rats undergoing 2-week perivascular suffusion of norepinephrine and adrenoceptor antagonists adjacent to the carotid artery, with or without balloon injury.

Intervention

Perivascular suffusion of norepinephrine and various adrenoceptor antagonists via microcatheter and osmotic minipump for 2 weeks

Outcome

Vascular wall growth (lumen area, adventitial area, circumference, neointimal area, collagen content)surrogate

This study provides the first in vivo evidence that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth via alpha-1A adrenoceptors.

Main Result

p-value: p=<0.05

Abstract

Previous studies suggesting that norepinephrine is directly trophic for the vascular wall have been confounded by concomitant hemodynamic disturbances. Herein, a microcatheter connected to an osmotic minipump was implanted adjacent to the rat carotid for 2-wk perivascular suffusion of agents at systemic levels ~1,000 times below the threshold for altering arterial pressure. Norepinephrine decreased lumen and adventitial areas and circumference by 10, 14, and 5%, respectively (all P < 0.05); a nonsubtype-specific alpha(1)-adrenoceptor (AR) antagonist had no effect. When begun at the time of balloon injury, 2-wk norepinephrine increased lumen loss by 45%, increased neointimal area by 64% and collagen content by 33%, and reduced vessel circumference by 5% (all P < 0.05). alpha(1)-AR antagonists decreased neointimal area by 33% (all P < 0.05). alpha(1)A-AR antagonist reduced lumen loss by 70%, neointimal area by 54%, circumference decline by 84%, and adventitial thickening by 87% (all P < 0.05), whereas alpha(1B)-, alpha(1D)-, alpha(2)- and beta-AR antagonists were without effect. These are the first in vivo studies demonstrating that norepinephrine is directly trophic for the vascular wall and augments injury-induced intimal lesion growth.

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