A Blunted Sympathetic Function and an Enhanced Nitrergic Activity Contribute to Reduce Mesenteric Resistance in Hyperthyroidism.

We aimed to determine whether an experimental model of hyperthyroidism could alter the function of sympathetic and nitrergic components of mesenteric innervation. For this purpose, male Wistar rats were divided into (1) control rats (CT) and (2) rats infused with L-Thyroxine (HT). Body weight gain and adipose tissue accumulation were lower in HT rats, while systolic blood pressure and citrate synthase activity in the soleus muscle were increased by HT. In segments from the superior mesenteric artery, the application of an electrical field stimulation (EFS) induced a vasoconstrictor response, which was lower in arteries from HT animals. The alpha-adrenoceptor antagonist phentolamine diminished EFS-induced vasoconstriction to a lower extent in HT arteries, while the purinergic receptor antagonist suramin reduced contractile response to EFS only in segments from CT. In line with this, noradrenaline release, tyrosine hydroxylase expression and activation and dopamine ß hydroxylase expression were diminished in HT. The unspecific nitric oxide synthase (NOS) inhibitor L-NAME increased EFS-induced vasoconstriction more markedly in segments from HT rats. NO release was enhanced in HT, probably due to an enhancement in neuronal NOS activity, in which a hyperactivation of both PKC and PI3K-AKT signaling pathways might play a relevant role. In conclusion, perivascular mesenteric innervation might contribute to reduce the vascular resistance observed in hyperthyroidism.

Using intravascular autoradiography for an estimation of proliferative activity of rat mesenteric microvessel endothelial cells during the first month of postnatal development.

BACKGROUND/METHODS: We applied a novel method for studying endothelial cells (EC) by using autoradiography of cells labeled by 3H-thymidine: photo emulsion was administered into the vascular bed. In the flat transparent organ, this method allows to compare the mitotic activity of endothelium (MAE) depending on vessel diameter and animal age. RESULTS: The number of the labeled ECs in animals was found to be almost equal in all vessels at the same age. The amount of labeled vessels and the density of the labeled nuclei increase towards near-capillary vessels of a diameter < or =10 microm. With age, MAE decreases in all categories of vessels. However, in 12-day-old animals, MAE temporarily increases. It was noted that high MAE in the bed of these rats precedes or coincides with the period of accelerated weight gain of the digestive system supplied by an increase in organ blood flow. CONCLUSIONS: By using the endothelial autoradiography method that we developed, we obtained the following evidence: (1) the number of ECs in the synthetic phase of the mitotic cycle in mesenterial vessels is approximately identical in animals of the same age, and (2) this number decreases with age, except during the period of accelerated organ growth, when MAE increases.

Effect of sustained mesenteric nerve stimulation on intestinal oxygenation in developing swine.

The effects of sustained mesenteric nerve stimulation on intestinal oxygenation were determined in 3- and 35-day-old swine. Studies were conducted in pentobarbital-anesthetized animals during free-flow or constant-flow perfusion. Square-wave stimuli sufficient to induce maximal resistance vessel constriction were applied to postganglionic periarterial mesenteric nerves and each stimulation was sustained until measured variables reached steady state. When vascular resistance data were analyzed without data transformation, autoregulatory escape of intestinal vascular resistance was more complete in 3- than in 35-day-old animals when the escape process was complete; however, expression of these data as escape indexes revealed a similar degree of escape in both age groups. In 35-day-old animals, (a-v)O2 increased during sustained nerve stimulation under free-flow conditions; under constant-flow conditions, (a-v)O2, 86Rb extraction, and capillary permeability-surface area product were lower at completion of the escape process compared with baseline. In 3-day-old swine, these variables remained unchanged from baseline. Intestinal O2 uptake was compromised by sustained nerve stimulation, and this effect was similar in both age groups. We conclude that sustained nerve stimulation reduces intestinal oxygenation to a similar degree in 3- and 35-day-old swine. It is important to note, however, that the response of 3-day-old swine may be dissimilar from that which occurs during immediate postnatal life; indeed, the intestinal hemodynamic response of swine less than or equal to 1 day old should not be extrapolated from the response of 3-day-old animals.

The peptidergic innervation of the developing mesenteric vascular bed in the rat.

We have followed the development of perivascular nerve fibres using antisera to substance P, calcitonin gene related peptide, neuropeptide Y and vasoactive intestinal polypeptide in the mesenteric vascular bed of developing Sprague-Dawley rats. The pattern and density of innervation appeared to be determined by one week of age. The pattern of innervation by SP- and CGRP-positive fibres was similar. The pattern of innervation by neuropeptide Y-containing fibres was distinct from that of SP and CGRP. The VIP-positive fibre plexus was sparse and irregular compared with the others examined. The density of innervation by all fibre types was highest in the jejunal arteries.

Age-related changes of noradrenergic innervation of rat splanchnic blood vessels: a histofluorescence and neurochemical study.

The influence of ageing on the noradrenergic innervation of superior mesenteric artery and vein, renal artery and vein, and portal vein was studied in male Wistar rats by means of catecholamine histofluorescence, image analysis techniques and high pressure chromatography with electrochemical detection. Old age was accompanied by a marked increase in the density of noradrenergic innervation and an increase of noradrenaline levels in superior mesenteric artery, renal artery, and portal vein. In contrast, no significant age-related changes were observed in the density of noradrenergic innervation or in noradrenaline levels in superior mesenteric and renal vein. The present data indicate that, at least in superior mesenteric and renal artery and portal vein, senescence is not accompanied by loss or by lack of change in the noradrenergic innervation as commonly believed to be the case in many vascular trees. On the basis of our findings it cannot be excluded that increased plasma catecholamine levels observed in senescence derive, in part, from perivascular sympathetic endings.