We recently showed that perivascular sensory nerves of mesenteric branch arteries express a receptor for extracellular Ca2+ (CaR), and reported data indicating that this CaR mediates relaxation induced by physiologic levels of Ca2+. We have now tested whether the perivascular sensory nerve CaR-linked dilator system is a local phenomenon restricted to the mesentery, or is present in other circulations. Vessels from the mesenteric, renal, coronary, and cerebral circulations were studied. Immunocytochemical analysis was performed using anti-CaR and anti-neural cell adhesion molecule (NCAM) antibodies. Wire myography was used to assess contraction and relaxation. Although perivascular nerves of all arteries stained for CaR protein, there were regional differences. A morphometric method used to estimate CaR positive nerve density revealed the following rank order: mesenteric branch artery > basilar artery = renal interlobar artery > main renal trunk artery > left anterior descending coronary artery. Vessels from the mesentery, renal, coronary, and cerebral circulations showed nerve-dependent relaxation in response to electrical field stimulation (EFS) when precontracted with serotonin in the presence of guanethidine. The degree of Ca2+-induced relaxation of mesenteric, renal, and cerebral arteries positively correlated with the magnitude of EFS-induced relaxation. In contrast, coronary arteries contracted at Ca2+ levels between 1.5 and 3 mmol L(-1), and relaxed to a small degree to 5 mmol L(-1) Ca2+. Thus, a functional perivascular sensory nerve CaR-linked dilator system is present to varying degrees in the mesenteric, renal, and cerebral circulations, but only to a very limited extent in the coronary circulation.