Anatomic distribution of autonomic neural tissue in the developing dog heart: II. Nonadrenergic noncholinergic innervation by calcitonin gene-related peptide-immunoreactive tissue.

We used immunocytochemical localization of calcitonin gene-related peptide (CGRP) to trace the ontogenesis and anatomic distribution of this component of nonadrenergic noncholinergic (NANC) innervation in fetal, neonatal, and mature canine hearts and autonomic ganglia which control cardiac function. Rare varicose CGRP-immunoreactive nerve processes were present in the heart during late gestation. Abundant CGRP-immunoreactive neural tissue in the neonate suggested a burst of NANC innervation around birth. Neonatal, 1-, and 2-month-old animals all had many varicose individual nerve processes in addition to processes within bundles; however, the density of all CGRP-immunoreactive tissue appeared to decrease during this stage of development. Similarly, there were relatively more varicose stained nerve processes in the epicardial ganglia and numerous CGRP-immunoreactive cells and smooth nerve processes in the stellate ganglia of the neonate, as compared with older animals. In the mature animal CGRP-immunoreactive neural tissue in the heart was more sparse and largely confined to heterogeneous nerve bundles in the epicardium. The extramural coronary arteries were virtually the only site of innervation by individual nerve processes; CGRP-immunoreactive neural tissue was not found adjacent to working cardiac muscle fibers. At all developmental stages, the area of the sinoatrial node was the primary focus of CGRP innervation, although the atrioventricular nodal region was also preferentially innervated. In general, the atria contained more CGRP-immunoreactive tissue than the ventricles, which were only sparsely innervated. The perinatal peak in density of CGRP-immunoreactive neural tissue with subsequent decline to reach the adult pattern suggests a developmental role for NANC innervation in the dog heart.