The influence of chloroethylclonidine-induced contraction in isolated arteries of Wistar Kyoto rats: alpha1D- and alpha1A-adrenoceptors, protein kinase C, and calcium influx.
BACKGROUND
It has recently been reported that chloroethylclonidine (CEC) elicited contraction in tail arteries (alpha(1A)-adrenoceptors) and aorta (alpha(1D)-adrenoceptors) from normotensive and spontaneously hypertensive rats (SHR). This study investigated the relationship between CEC-induced contraction and the role of protein kinase C (PKC) and extracellular Ca(++) influx in tail arteries and aorta from Wistar Kyoto rats (WKY).


METHODS
Time-course of CEC-induced contraction in endothelium-denuded arteries from Wistar, WKY, and SHR rats was evaluated. In WKY arteries, calphostin C (1 x 10(-6) M) and nitrendipine (1 x 10(-6) M) were used to determine the role of PKC and extracellular Ca(+1) in the contractile response to CEC, respectively.


RESULTS
Chloroethylclonidine (1 x 10(-4) M) elicited contraction in tail arteries and aorta from normotensive and hypertensive rats. Maximal response to CEC was similar in tail arteries among strains (approximately 30% of norepinephrine effect), while in aorta CEC elicited a higher contraction in WKY and SHR than in Wistar (59, 86, and 18% of norepinephrine effect, respectively). CEC-elicited maximal contractile responses were reached in 5 min in tail arteries and in 30-45 min in aorta irrespective of the rat strain, suggesting that different intracellular signaling pathways are involved in the contractile response to CEC in these arteries. In WKY tail arteries, calphostin C and nitrendipine blocked CEC-induced contraction while in aorta nitrendipine, but not calphostin C, inhibited CEC action.


CONCLUSIONS
This study confirms marked strain-dependent differences in rat aorta responsiveness to CEC and suggests a central role for PKC in response to CEC in tail arteries and for extracellular Ca(+1) influx in aorta.
Ibarra
M
M
Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV del IPN), Mexico City, Mexico. maxibarrab@correo.unam.mx
López-Guerrero
J J
JJ
Villalobos-Molina
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects; D001158:Arteries / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009928:Organ Specificity; D011433:Propranolol / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects* / Q000502:physiology; D013045:Species Specificity; D013623:Tail / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
C547715:Adra1a protein, rat; C547721:Adra1d protein, rat; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D015016:Yohimbine; C051731:chlorethylclonidine; D009568:Nitrendipine; D011433:Propranolol; D011493:Protein Kinase C; C058819:calphostin C; D003000:Clonidine; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine