Effect of protein kinase C and protein kinase A inhibitors on contraction of isolated femoral arteries of SHR and Wistar rats.
Alterations of calcium handling and other second messenger cascades including protein kinase C (PKC) and A (PKA) were suggested to be responsible for abnormal vascular function in spontaneously hypertensive rats (SHR). However, the relative contribution of these pathways to vasoconstriction is still not completely understood. We investigated the effect of Ro 31-8220 (PKC inhibitor) and H89 (PKA inhibitor) on vasoconstriction induced by 120 mM KCl or by addition of 10 microM noradrenaline (NA) in isolated femoral arteries of control Wistar rats and SHR. Moreover, we investigated these responses in the presence and absence of Ca(2+) ions in the incubation medium in order to assess the role of calcium influx in these contractions. We observed that while the vasoconstriction in the presence of calcium was not different between Wistar and SHR, the difference between constriction elicited by NA addition in the absence and presence of external calcium was larger in SHR. The inhibition of PKC had no effect on constrictions in SHR, but diminished constrictions in Wistar rats. PKA inhibition slightly enhanced constrictions in Wistar rats, but reduced them in the presence of calcium in SHR. We conclude that vasoconstriction elicited by adrenergic stimulation is more dependent on extracellular calcium influx in SHR compared to Wistar rats. Moreover, the activation of PKA contributes to this calcium-dependent vasoconstriction in SHR but not in Wistar. On the other hand, PKC activation seems to play a less important role in vasoconstriction in SHR than in Wistar rats.
Bal
M S
MS
University of Texas Health Science Center, San Antonio, Texas, USA.
Paulis
L
L
Zicha
J
J
Kunes
J
J
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004195:Disease Models, Animal; D005263:Femoral Artery / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D006973:Hypertension / Q000201:enzymology* / Q000503:physiopathology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D007211:Indoles; D007546:Isoquinolines; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D002118:Calcium; C064758:Ro 31-8220; D009638:Norepinephrine