Carvedilol, a new beta-adrenoreceptor blocker antihypertensive drug, protects against free-radical-induced endothelial dysfunction.
We tested the ability of carvedilol, an antihypertensive beta-adrenoreceptor antagonist with antioxidant properties, to protect rat aorta rings from free-radical-induced endothelial cell (EC) dysfunction. Rings were exposed to the superoxide generator pyrogallol. Vascular function of intact rings was assessed by observing acetylcholine (ACh)-induced vasorelaxation following submaximal contraction by U-46619. Function of rings denuded of ECs was assessed by observing S-nitroso-N-acetylpenicillamine (SNAP)-induced vasorelaxation following submaximal contraction by U-46619. Carvedilol exerted a significant protective effect against pyrogallol-induced vasoconstriction (17.1 +/- 4.8 vs. 31.9 +/- 5.4% for vehicle, p < 0.05). Carvedilol also demonstrated significant protection against pyrogallol-induced endothelium dysfunction, enhancing vasorelaxation to 1,000 nmol/l ACh (73 +/- 3.9 vs. 48 +/- 3.0% vehicle, p < 0.01). These protective effects were not seen with propanolol, a pure beta-receptor antagonist. Carvedilol mixed with pyrogallol and SNAP preserved SNAP-induced vasorelaxation in rings denuded of ECs (80.4 +/- 5.3 vs. 63.7 +/- 4.8% control, p < 0.05). Carvedilol appears to protect vascular function by scavenging free radicals and enhancing the effects of NO.
Lopez
B L
BL
Department of Surgery, Jefferson Medical College, Thomas Jefferson University Hospital, Philadelphia, PA 19107-5004, USA.
Christopher
T A
TA
Yue
T L
TL
Ruffolo
R
R
Feuerstein
G Z
GZ
Ma
X L
XL
D000109:Acetylcholine / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005609:Free Radicals / Q000633:toxicity; D066298:In Vitro Techniques; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology*; D011748:Pyrogallol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D002227:Carbazoles; D005609:Free Radicals; D011412:Propanolamines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D011748:Pyrogallol; D000077261:Carvedilol; D013481:Superoxides; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D000109:Acetylcholine