Influence of extracellular calcium and nifedipine on α1-and α2-adrenoceptor-mediated contractile responses in isolated rat and cat cerebral and mesenteric arteries

The influence of extracellular Ca²⁺ and nifedipine on contractile responses to 10 μM noradrenaline (NA) was investigated in isolated rat and cat middle cerebral (RCA, CCA) and mesenteric (RMA, CMA) arteries. In the CCA (containing predominantly α₂-adrenoceptors), the NA-induced contractions developed considerably more slowly than in the RCA, RMA (containing mainly α₁-adrenoceptors) and CMA (sensitive to both at,- and α₂-adrenoceptor selective antagonists). The tonic component of the NA-induced contraction in the four types of artery was substantially suppressed after only short periods in Ca²⁺-free solution. In each type of artery, excluding the CCA, the contractile response to 124 mM K⁺ was more sensitive to Ca²⁺ deprivation than that to NA. This suggests that NA, besides mobilizing extracellular Ca²⁺, can also release Ca²⁺ from an intracellular pool in the RCA, RMA and CMA, but not in the CCA. Thus, α₁-adrenoceptor-mediated contractions in the RCA and RMA seem to depend on both Ca²⁺ influx and intracellular Ca²⁺ release, whereas α₂-adrenoceptor-mediated contractile responses in the CCA appear to rely almost entirely on Ca²⁺ influx. Both the maximum response and the tonic component of the NA-induced contraction were significantly more sensitive to nifedipine in the CCA than in the RCA. In comparison with the NA-induced contractions in these arteries, those in the RMA and CMA were relatively resistant to nifedipine. In the CCA exposed to NA in Ca²⁺-free medium, nifedipine almost abolished the contraction induced by re-addition of Ca²⁺, whereas in the other types of artery, Ca²⁺ re-application evoked a significant contraction also in the presence of the drug. The differential effects of nifedipine presumably reflect differences between the arteries, not only in the relative contribution of Ca²⁺ influx and intracellular Ca²⁺ release to the contractile activation, but also in the nifedipine sensitivity of the Ca²⁺ entry pathways utilized by NA. It is concluded that the mechanisms through which NA induces contraction seem to be related both to the subtype of α-adrenoceptor stimulated by NA and to the type of vessel studied.