Sarcoplasmic reticulum Ca²⁺ uptake is not decreased in aorta from deoxycorticosterone acetate hypertensive rats: Functional assessment with cyclopiazonic acid

Ca²⁺ plays a major role in vascular contraction, and a defect in intracellular Ca²⁺ regulation has been associated with increased vascular reactivity in hypertension. To test the hypothesis that the sarcoplasmic reticulum does not adequately buffer Ca²⁺ in deoxycorticosterone acetate (DOCA) hypertension, contractile experiments were performed with a specific inhibitor of the sarcoplasmic reticulum Ca²⁺ ATPase, cyclopiazonic acid (CPA). Contractile force in aortic strips from DOCA and control rats was measured, using standard muscle bath procedures, to evaluate (i) Ca²⁺ handling, assessing caffeine and serotonin (5HT) induced contractions in Ca²⁺-free buffer and (ii) relaxation rate after 5HT washout. Contractile responses elicited with 5HT (3 x 10^-6 mol/L) and 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 5HT and caffeine in DOCA and control aorta, and no differences in the IC₅₀ 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 contraction did not occur in Ca²⁺-free buffer, and it was inhibited by nifedipine (IC₅₀ = 4 x 10^-9 mol/L). The relaxation rate, after 5HT washout (3 x 10^-6 mol/L), was increased in DOCA aorta (2.6 ± 0.3 min) compared with control (17 ± 0.2 min), and CPA (10^-5 mol/L) increased the relaxation rate in both groups. The results support the hypothesis of defective Ca²⁺ handling in DOCA hypertension. However, an increased Ca²⁺ influx, and not a decreased buffering ability of the sarcoplasmic reticulum, contributes to the enhanced vascular reactivity observed in DOCA hypertension.