Distribution of the vasoconstrictor and vasorelaxant effects of norbormide along the vascular tree of the rat.
Norbormide is a vasoconstrictor of rat peripheral arteries and a relaxant in rat aorta. To characterise norbormide actions within the rat vascular tree we have investigated its effects on the contractile function of rings from several arteries and veins. A maximal norbormide concentration (50 microM) failed to contract thoracic aorta and carotid artery, whereas in pulmonary artery, abdominal aorta, iliac, caudal, and femoral arteries it induced a contractile effect that was respectively 4.8 +/- 0.6, 18.4 +/- 1.5, 39 +/- 5, 144 +/- 7, and 260 +/- 22% of that induced by 90 mM KCl. In pulmonary, carotid, and iliac arteries, and in thoracic and abdominal aorta, 50 microM norbormide inhibited KCl-induced responses. Norbormide (50 microM) contracted all veins investigated. The effect, expressed as % of KCl-induced contraction, was 121 +/- 25, 154 +/- 14.5, 154 +/- 18.2, 203 +/- 19, and 267 +/- 33 for pulmonary vein, thoracic and abdominal vena cava, iliac and jugular veins, respectively. In jugular vein, as previously shown in rat caudal artery, norbormide contraction was abolished in Ca2+-free medium, was unaffected by the Ca2+ channel blocker nifedipine, and was relaxed by SK&F 96365, a blocker of store-operated Ca2+ channels.


CONCLUSIONS
i) rat veins represent the main target for contractile norbormide action; ii) in both artery and veins norbormide contractions are generally inversely related to the calibre of the vessel; iii) norbormide-induced contraction is mediated by the same mechanism/s in arteries and veins; iiii) in norbormide-contracted arteries the drug activates both contractile and relaxing mechanisms.
Cavalli
Maurizio
M
Dipartimento di Farmacologia ed Anestesiologia, Università degli Studi di Padova, Largo E. Meneghetti 2, 35131 Padova, Italy.
Omiciuolo
Luisella
L
Cargnelli
Gabriella
G
Cima
Lorenzo
L
Hopkins
Brian
B
Bova
Sergio
S
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D007537:Isometric Contraction; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D009636:Norbornanes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*; D014680:Veins / Q000187:drug effects
D002121:Calcium Channel Blockers; D007093:Imidazoles; D009636:Norbornanes; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D009543:Nifedipine; C005321:norbormide