Mechanism of enhanced calcium sensitivity and alpha 2-AR vasoreactivity in chronic NOS inhibition hypertension.
PKC augments calcium sensitivity in spontaneously hypertensive rats and contributes to alpha(2)-adrenergic receptor (AR) contraction in rabbit saphenous vein. We showed previously that denuded aortic rings from N(omega)-nitro-l-arginine-treated hypertensive rats (LHR) contract more to CaCl(2) and to the alpha(2)-AR agonist UK-14304 than do rings from normotensive rats (NR). We hypothesized that enhanced PKC activity or a change in PKC isoform contributes to augmented calcium sensitivity and enhanced alpha(2)-AR contraction in LHR aorta. Current studies demonstrate that non-isoform-specific PKC inhibitors reduced UK-14304 contraction in both NR and LHR aorta. However, the calcium-dependent PKC inhibitor Gö-6976 only attenuated contraction in LHR aorta. Additionally, UK-14304 translocated PKC-delta to the membrane in NR aorta, whereas PKC-alpha was translocated to the membrane in LHR aorta. Finally, in ionomycin-permeabilized aorta Gö-6976 eliminated enhanced basal and augmented alpha(2)-AR-stimulated calcium sensitivity in LHR aorta but did not affect NR contraction. Together, these data suggest that PKC-alpha contributes to augmented calcium sensitivity and alpha(2)-AR reactivity after chronic nitric oxide synthase inhibition hypertension.
Carter
Rebecca W
RW
Department of Cell Biology and Physiology, University of New Mexico Health Sciences Center, Albuquerque 87131-5218, USA. bcarter@salud.unm.edu
Kanagy
Nancy L
NL
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002908:Chronic Disease; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D014661:Vasoconstriction / Q000502:physiology; D014666:Vasomotor System / Q000503:physiopathology*
D018341:Receptors, Adrenergic, alpha-2; D019335:Nitroarginine; D019001:Nitric Oxide Synthase; D011493:Protein Kinase C; D002118:Calcium