Influence of humoral control peptides on medullary vasomotor control neurons: microstimulation and double-labeling studies using SHR and WKY rats.

To study the influence of humoral control peptides on medullary vasomotor control neurons, angiotensin II (AII), arginine vasopressin (AVP) and atrial natriuretic peptide (ANP) were microinjected into three vasomotor control areas, i.e., the area postrema (AP), the nucleus tractus solitarii (NTS) and the rostral ventrolateral medulla (RVLM), of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY), and the evoked cardiovascular response was observed. Unlike the injection areas, the threshold dose of one peptide for the cardiovascular response was similar, but the threshold dose differed from peptide to peptide. The threshold dose was lower for AII (0.15-0.29 pmol), in-between for ANP (0.9-1.5 pmol) and higher for AVP (14-30 pmol). No significant difference in the threshold dose was observed between SHR and WKY, suggesting that hypertension in SHR may not be due to the abnormal sensitivity to the three peptides of the vasomotor control neurons in the AP, NTS, and RVLM. The structural basis of the results of the microstimulation experiment was supported by the double-labeling study. The NTS neurons were innervated by (1) the AII-immunoreactive (ir) neurons in both sides of the lateral hypothalamic area (LH), the RVLM and the caudal ventrolateral medulla, and (2) the ANP-ir neurons in both sides of the paraventricular nucleus (Pa) and the LH. The RVLM neurons were innervated by (1) the AII-ir neurons in both sides of the LH and ipsilateral side of the lateral parabrachial nucleus (Pbl) and (2) the ANP-ir neurons in the ipsilateral Pbl. There was no evidence that the AVP-ir neurons in the Pa and the supraoptic nucleus innervate the NTS and the RVLM neurons, or that the AII, ANP or AVP-ir neurons innervate the AP neurons. This study suggests that in common with SHR and WKY rats AII and ANP may influence both the NTS and RVLM not by the humoral pathway but by the neural pathway, and AVP may not influence the three vasomotor control areas by the neural pathway.