Nucleus tractus solitarius (NTS), an aggregate of several individual nuclear groups in the dorsal medulla oblongata, is involved in virtually all autonomic functions as the first synaptic site in the brain for many peripheral viscerosomatic inputs. We found morphological evidence that dorsocaudal subregions of rat NTS (approximately 800 microns caudal from obex) had fenestrated capillaries and enlarged Virchow-Robin (perivascular) spaces that were similar to those in area postrema but unlike capillaries elsewhere in the medulla oblongata. Complexes of microvessels, consisting of up to 10 small vessels with smooth muscle layers (luminal diameters of 10-45 microns) and several capillaries (average luminal diameter of 4.5 microns), were located in the dorsal midline of NTS within large Virchow-Robin spaces measuring some 2,000 microns 2 in area. In physiological studies, we determined that most of NTS had a definable blood-brain barrier [permeability-surface area (PS) products for a neutral amino acid near 0], but medial and lateral aspects of the commissural subnucleus of NTS had PS products of 16-63 microliters.g-1.min-1 for alpha-[14C]aminoisobutyric acid 12 s after intravenous injection. Microvascular differentiations permitting such brisk tracer influx from blood resemble those of area postrema and appear to afford the rich neuropil of commissural NTS with a constant stream of blood-borne information for expediting its regulation of viscerosensory and autonomic functions.

The differentiated cytology, cytochemistry, and functions within subdivisions of the tuber cinereum prompted this morphometric and physiological investigation of capillaries in the medium eminence and arcuate nucleus of albino rats. Morphometric studies established that the external zone of the median eminence had 3-5 times the number and surface area of true and sinusoidal capillaries than the internal or subependymal median eminence zones, or either of two subdivisions examined in the arcuate nucleus. Type-I true capillaries, around which Virchow-Robin spaces comprise 1% of arcuate tissue area, were situated proximally to the median eminence border. This finding is consistent with a premise that confluent pericapillary spaces enable infiltration of arcuate neurons by factors from capillary blood from the median eminence or Virchow-Robin spaces. Physiologically, the rate of penetration across the median eminence capillaries by blood-borne [14C]alpha-amino-isobutyric acid (a neutral amino acid used as a capillary permeability tracer) was 142 times greater than for capillaries in the distal arcuate nucleus within 12 s of tracer administration. A new finding was that the proximal arcuate nucleus had a permeability x surface area product of 69 microliters g-1 min-1, 34 times greater than that in more distal aspects of the tuber where blood-brain barrier properties exist. We also found that the microcirculatory transit time of a plasma space marker, [14C]sucrose, was considerably longer (1.2 s) in the median eminence and proximal arcuate nucleus than in the distal arcuate or ventromedial nucleus (0.4 s). By virtue of its high capillary permeability and extensive blood-tissue surface area, including the wide Virchow-Robin spaces, the median eminence external zone could be a gateway for flooding other tuberal compartments with blood-borne factors. This effect may be compounded by capillary bed specializations in the proximal arcuate nucleus where Type-I true capillaries, Type-III sinusoids, and pericapillary spaces are confluent with those in the median eminence. The results indicate that the proximal arcuate parenchyma could be exposed to circulating neuroactive substances on a moment-to-moment basis.

Angiotensin II (ANG II) acts peripherally as a hormone, with actions on the vasculature, adrenals, and kidney. In addition, certain actions of ANG II in the central nervous system are directed toward cardiovascular control and fluid volume homeostasis. Dense binding sites for ANG II are found at circumventricular organs, which apparently have the ability to relay information to cardiovascular centers via neural circuitry. Microinjection of ANG II into the subfornical organ (SFO) or area postrema (AP) produces site-specific increases in blood pressure. In addition, electrophysiological studies demonstrate profound effects of ANG II, acting at the SFO, on activity of neurohypophysial neurons and release of oxytocin and vasopressin, which can be antagonized by ANG II blockers or attenuated by SFO lesions. Evidence from microinjection, electrophysiological, and lesion studies indicate a complex interaction between central sites involved in mechanisms of cardiovascular control: the SFO, AP, organum vasculosum of the lamina terminalis, and paraventricular and supraoptic nuclei of the hypothalamus. Not only is ANG II a humoral messenger in this central scenario, but evidence suggests it acts as a neurotransmitter or neuroendocrine substance within specific CNS pathways, suggesting multiple roles for this peptide in central cardiovascular control.

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