SARCOPLASMIC-RETICULUM CA2- FUNCTIONAL ASSESSMENT WITH CYCLOPIAZONIC ACID( UPTAKE IS NOT DECREASED IN AORTA FROM DEOXYCORTICOSTERONE ACETATE HYPERTENSIVE RATS )

Ca2+ plays a major role in vascular contraction, and a defect in intra cellular Ca2+ regulation has been associated with increased vascular r eactivity in hypertension. To test the hypothesis that the sarcoplasmi c reticulum does not adequately buffer Ca2+ in deoxycorticosterone ace tate (DOCA) hypertension, contractile experiments were performed with a specific inhibitor of the sarcoplasmic reticulum Ca2+ ATPase, cyclop iazonic acid (CPA). Contractile force in aortic strips from DOCA and c ontrol rats was measured, using standard muscle bath procedures, to ev aluate (i) Ca2+ handling, assessing caffeine and serotonin (5HT) induc ed contractions in Ca2+-free buffer and (ii) relaxation rate after 5HT washout. Contractile responses elicited with 5HT (3 x 10(-6) mol/L) a nd caffeine (20 mmol/L) were greater in DOCA than in control arteries. CPA (1 x 10(-7) to 3 x 10(-5) mol/L) reduced phasic contractions to 5 HT and caffeine in DOCA and control aorta, and no differences in the I C50 values were observed. Aortae from DOCA rats contracted when placed in normal buffer, subsequent to treatment with Ca2+-free buffer, but control aortae did not. CPA potentiated these responses in DOCA aorta and only caused a modest contraction in control aorta. CPA-induced con traction did-not occur in Ca2+-free buffer, and it was inhibited by ni fedipine (IC50 = 4 x 10(-9) mol/L). The relaxation rate, after 5HT was hout(3 x 10(-6) mol/L), was increased in DOCA aorta (2.6 +/- 0.3 min) compared with control (1.7 +/- 0.2 min), and CPA (10(-5) mol/L) increa sed the relaxation rate in both groups. The results support the hypoth esis of defective Ca2+ handling in DOCA hypertension. However, an incr eased Ca2+ influx, and not a decreased buffering ability of the sarcop lasmic reticulum, contributes to the enhanced vascular reactivity obse rved in DOCA hypertension.