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 leading cause of death in patients with chronic kidney disease (CKD) is cardiovascular disease, with vascular calcification being a key modifier of disease progression. A local regulator of vascular calcification is vitamin K. This γ-glutamyl carboxylase substrate is an essential cofactor in the activation of several extracellular matrix proteins that inhibit calcification. Warfarin, a common therapy in dialysis patients, inhibits the recycling of vitamin K and thereby decreases the inhibitory activity of these proteins. In this study, we sought to determine whether modifying vitamin K status, either by increasing dietary vitamin K intake or by antagonism with therapeutic doses of warfarin, could alter the development of vascular calcification in male Sprague-Dawley rats with adenine-induced CKD. Treatment of CKD rats with warfarin markedly increased pulse pressure and pulse wave velocity, as well as significantly increased calcium concentrations in the thoracic aorta (3-fold), abdominal aorta (8-fold), renal artery (4-fold), and carotid artery (20-fold). In contrast, treatment with high dietary vitamin K1 increased vitamin K tissue concentrations (10-300-fold) and blunted the development of vascular calcification. Thus, vitamin K has an important role in modifying mechanisms linked to the susceptibility of arteries to calcify in an experimental model of CKD.

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.

Introduction Aging increases the risk of both erectile dysfunction (ED) and cardiovascular disease. These conditions have similar etiologies and commonly coexist. One unifying concept is the role of arterial insufficiency which is a primary factor in the onset of age-related ED. Aim Based on the novel finding that the pudendal arteries contribute 70% of the total penile vascular resistance, our objective was to morphometrically and functionally characterize this vessel in young and old normotensive rats. Methods Erectile function was monitored in 15- and 77-week Sprague-Dawley rats using the apomorphine bioassay (80 mg/kg, s.c.). Anesthetized animals were perfusion-fixed, aortic, renal, and internal pudendal arteries were excised, embedded, sectioned, stained, and morphometrically assessed using light microscopy. Hearts were excised, separated, and weighed prior to perfusion. Contractile and relaxation responses to acetylcholine (ACh) and phenylephrine (PE) were assessed by wire myograph. Main Outcome Measures Erectile function, morphological measurements, concentration response curves to ACh and PE. Results With age, there were marked decreases in erectile responses compared to younger rats (2.8 ± 0.87 vs. 0.3 ± 0.58). The pudendal arteries had a relatively small lumen (303 ± 13.8 µm) and a thick medial layer (47 ± 2.2 µm). In aged pudendal arteries, the lumen diameter did not change, and yet the medial layer, cross sectional area, and extracellular matrix were markedly increased. In contrast, the lumen diameter and wall thickness of the aorta and renal arteries in aged rats increased proportionally. An increase in small, round, smooth muscle cells was seen in aged pudendal arteries. Functionally, there were no differences in contractile responses to PE; however, ACh-induced relaxation decreased with age. Conclusions In aged rats, erectile function was severely diminished when pudendal arteries had undergone marked phenotypic changes. Specifically, there was endothelial dysfunction and pathological remodeling of this vessel with age, characterized by medial thickening, impaired vasodilation and significantly reduced capacity for penile blood flow.