E. Weihe

Peptidergic innervation of the mammalian sinus nodes: Vasoactive intestinal polypeptide, neurotensin, substance P

By the use of the peroxidase--antiperoxidase (PAP) technique in the sinus node of several mammalian species, vasoactive intestinal polypeptide (VIP), neurotensin (NT) and substance P (SP) immunoreactive structures were detected. VIP and NT as well as SP immunoreactive fibers were found in close association to the vasculature. While the innervation by SP immunoreactive fibers was restricted to blood vessels, VIP and NT immunoreactive fibers and varicosities were also in contact to nodal cells. Juxtanodal intracardiac ganglia and single intranodal ganglionic cells were supplied by VIP, NT and SP immunoreactive varicosities. In addition, VIP immunoreactive perikarya were present. The results suggest an involvement of VIP, NT and SP in the regulation of sinus node blood flow, in impulse generation as well as in extrinsic and intrinsic cardiac reflex mechanisms.

Distribution of vasoactive intestinal polypeptide-like immunoreactivity in the mammalian heart

SummaryThe distribution of vasoactive intestinal polypeptide (VIP) immunoreactivity has been studied in the mammalian heart and compared with that of neurotensin and substance P by use of light-microscopic peroxidase-antiperoxidase immunohistochemistry. VIP-immunoreactive cell bodies are present in intracardiac ganglia in various locations. VIP-immunoreactive nerve fibers predominate in the atria and the conduction system but are rare in the ventricles and occur in cardiac ganglia, endocardium, and epicardium. VIP-ergic nerves supply the coronary vasculature having a preference for the microvasculature and the nodal cells of the sinuatrial node. The large vessels of the heart and periarterial cardiac glomera also receive a VIP-immunoreactive nerve supply. There is partial co-distribution with neurotensin- and substance P-immunoreactive nerve fibers but no co-location in identical nerve fibers is detectable. The VIP-ergic cardiac innervation, which is probably predominantly intrinsic, may stem from postganglionic parasympathetic neurons and is less substantial than the more homogeneous neurotensin-ergic and substance P-ergic nervous supply which is probably extrinsic. The occurrence of an extrinsic VIP-ergic cardiac innervation cannot be excluded however. The differential histotopography of the multitarget cardiac nerves containing the cardiovascular active peptides VIP, neurotensin and substance P may suggest multiple and complex peptide-peptide and peptide-classical transmitter interactions. These may contribute to the regulation of various cardiac functions.

Substance P-immunoreactive nerve fibers in the heart

Abstract By the use of the peroxidase-antiperoxidase (PAP) technique substance P (SP)-immunoreactive nerve fibers and varicosities were identified in the adventitial layers of the aorta, the pulmonary trunk and the coronary arteries and veins in the guinea pig heart. The results suggest an involvement of SP-innervation in the regulation of coronary blood flow.

Dopamine-β-hydroxylase-, neurotensin-, substance P-, vasoactive intestinal polypeptide- and enkephalin-immunohistochemistry of paravertebral and prevertebral ganglia in the cat

SummaryPara and prevertebral ganglia of the cat were investigated for immunoreactivity (IR) against neurotensin (NT), vasoactive intestinal polypeptide (VIP), substance P (SP) and enkephalin (ENK). Dopamine-β-hydroxylase- (DBH)-IR was studied in consecutive sections to correlate the distribution of noradrenergic/adrenergic neurons with that of peptidergic nerve fibres and cells.In paravertebral (cervical and thoracic) ganglia, NT-IR or ENK-IR nerve fibres were seen in areas in which DBH-IR fibre networks also occurred. NT-IR varicosities were often in close contact with perikarya of principal ganglionic cells on which DBH-IR varicosities also terminated. Such an association was rarely seen between ENK-IR and DBH-IR fibre baskets. NT-IR and ENK-IR fibre baskets were not found to occur around the same principal ganglionic cell. The distribution of VIP-IR and SP-IR nerve fibres did not coincide with that of DBH-IR fibres.In prevertebral ganglia (celiac-superior mesenteric and inferior mesenteric) DBH-IR or VIP-IR varicosities surrounded the majority of principal ganglionic neurons. ENK-IR or SP-IR fibres were closely associated with only a minority of the neurons; NT-IR networks were rather sparse. Some principal neurons were approached by DBH-IR fibres and by different peptide-IR fibres.In paravertebral ganglia some principal ganglionic cells contained VIP-IR, a few of which were also surrounded by NT-IR varicosities. VIP-IR perikarya in prevertebral ganglia were extremely rare. No NT-IR, SP-IR or ENK-IR principal ganglionic cells were found.Glomus-like paraganglionic cell clusters in paravertebral and prevertebral ganglia exhibited DBH-IR cell bodies. Moreover, the clusters also contained ENK-IR or SP-IR cells. NT-IR varicosities were observed adjacent to clustered paraganglionic cells. Only few singly located paraganglionic cells were NT-IR or ENK-IR.The differential distribution of peptide-IR nerve endings in the investigated ganglia suggests a regulation of impulse transmission that seems to be related to the target organs.

Localization of neurotensin immunoreactive nerve fibers in the guinea-pig heart: Evidence derived by immunohistochemistry, radioimmunoassay and chromatography

By the use of the peroxidase-antiperoxidase technique guinea-pig hearts were investigated for the occurrence of neurotensin immunoreactivity. Neurotensin immunoreactive nerve fibers were found in distinct localisations in all hearts studied. In addition, neurotensin immunoreactive fibers were present in the adventitia of the ascending aorta, the aortic arch and the pulmonary trunk. All segments of the coronary vasculature exhibited a dense network of neurotensin immunoreactive fibers. This innervation pattern was most pronounced in the arterial portions. Neurotensin immunoreactive fibers occurred also in close contact with atrial and ventricular muscle cells. A particularly dense innervation by neurotensin immunoreactive fibers was present in the sinu-atrial node and in the atrio-ventricular node. The fibers were associated intimately with blood vessels as well as with nodal cells. In addition, neurotensin immunoreactive fibers were found in intracardiac ganglia. The presence of neurotensin-like immunoreactive material in the guinea-pig heart was demonstrated also by radioimmunoassay. The results of immunohistochemistry and radioimmunoassay were correlated. High performance liquid chromatographic analysis indicated that 20-30% of the total immunoreactivity co-chromatographed with guinea-pig or synthetic neurotensin. Evaluation of consecutive sections revealed different innervation patterns of neurotensin and substance P immunoreactive fibers. The findings suggest a neurotransmitter and/or neuromodulator function of neurotensin in the regulation of coronary circulation, of cardiac impulse generation and conduction, of heart muscle contractility and of cardiac reflex mechanisms. It is speculated that neurotensin might represent the efferent and substance P the afferent part of a cardiac regulatory system.

Neurotensin and Substance P Immunoreactive Nerve Endings in the Guinea Pig Carotid Sinus and Their Ultrastructural Counterparts

SummaryThe carotid sinus of the guinea pig was analysed immunohistochemically for the occurrence of neuropeptides. Immunoreactivity (IR) for neurotensin (NT) and substance P (SP) is distributed in two different populations of nerve endings and varicosities. NT-IR fibers penetrate deeply into the tunica media of the elastic segment of the carotid sinus and form the large, branched lanceolate nerve terminals. Electron-microscopic investigations have revealed that the NT-IR varicosities correspond to the large afferent baroreceptor endings containing abundant mitochondria. SP-IR fibers are located mainly at the mediaadventitial border. They seem to be correlated to dense-core, vesiclecontaining varicosities identified in the electron microscope. Therefore, these fibers may constitute afferent and efferent perivascular plexus regulating the vascular tone of the carotid sinus wall.

SCANNING ELECTRON MICROSCOPY OF ENDOTHELIUM

In this study the endothelial surface of dog heart coronary system and micro- and macrovascular segments of the rat were investigated by scanning electron microscopy. In rats the effects of varying perfusion pressure, application of rinsing solutions, and age of animals were analyzed. Comparison of endocardial surfaces from dogs and rats showed regional differences of valvular, trabecular, and nonvalvular ventricular and atrial endocardium without significant species differences. Short rinsing times by perfusing an electrolyte solution containing procaine did not effect the homogenity of total endocardial and vascular surface structure. Variations of perfusion pressure effected endothelial surface relief. Low perfusion pressures produced contraction folds and high perfusion pressures (200 mm Hg) small holes and monocellular furrowing in the macrovasculature. In the microvasculature higher pressures caused an increased diameter of fenestrations of liver sinusoids, but no effect on continuous capillary endothelium. Segmental variations in the rat aorta were consistent findings. Crater-like depressions in the endothelium of rat aorta were interpreted as typical aging effects. The endothelium of branches from the right and left coronary arteries from dog hearts exhibited typical elongated cells with a smooth surface.