Brainstem phosphorylated extracellular signal-regulated kinase 1/2-nitric-oxide synthase signaling mediates the adenosine A2A-dependent hypotensive action of clonidine in conscious aortic barodenervated rats.

The cellular mechanisms that underlie the enhancement of clonidine-evoked hypotension in aortic barodenervated (ABD) rats and its dependence on central adenosine A(2A) receptor (A(2A)R) are not known. We tested the hypothesis that A(2A)R-mediated phosphorylation of extracellular signal-regulated kinase (pERK)1/2 in the rostral ventrolateral medulla (RVLM) and its downstream activation of nitric-oxide synthase (NOS)-NO signaling underlie the centrally (clonidine)-mediated hypotension. We first demonstrated an up-regulation of the molecular targets for clonidine [imidazoline I(1) and alpha(2A) adrenergic receptors (alpha(2A)R)] in the RVLM of ABD compared with sham-operated (SO) rats; this finding might explain the enhanced clonidine hypotension in ABD rats. A similar anatomical up-regulation of the RVLM A(2A)R was evident and was complemented with enhanced central A(2A)R [2-[4-[(2-carboxyethyl)phenyl]ethylamino]-5'-N-ethylcarboxamidoadenosine; CGS21680]-mediated hypotension in ABD rats. The hypotension produced by intracisternal CGS21680 or clonidine, in conscious ABD rats, was associated with a significant increase in pERK1/2 level in the RVLM. Whereas selective A(2A)R blockade [5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo[4,3-epsilon]-1,2,4-triazolo[1,5-c]pyrimidine; SCH58261] or NOS inhibition (N(omega)-nitro-l-arginine methyl ester) virtually abolished clonidine-evoked hypotension, clonidine-evoked enhancement of RVLM pERK1/2 production was only abrogated by SCH58261 pretreatment. These findings suggest that interventions that act centrally to increase RVLM neuronal pERK1/2 production elicit hypotension via the activation of downstream NOS-NO signaling. The findings also yield insight into a cellular mechanism that might explain the dependence of centrally (clonidine)-mediated hypotension on central A(2A)R signaling in the ABD rat.

Blood pressure variability provokes vascular ß-adrenoceptor desensitization in rats.

Spontaneous variation in blood pressure is defined as 'blood pressure variability' (BPV). Sinoaortic denervation (SAD) is characterized by BPV without sustained hypertension. In the present study, we investigated whether BPV could be related to vascular ß-adrenoceptor desensitization in rats. Three days after surgery (SAD and control), aortic rings were placed in an organ chamber and the relaxation stimulated by ß-adrenoceptor agonists, isoprenaline, terbutaline, BRL37344 and cyanopindolol was verified. The participation of intracellular nucleotides signaling pathways was also verified using forskolin, sodium nitroprusside and acetylcholine to induce relaxation. The effects of BPV on the increase in endothelial cytosolic Ca(2+) concentration stimulated by the ß2-adrenoceptor agonist was examined by confocal microscopy. In addition, the vascular expression of the ß2-adrenoceptor was also examined by immunohistochemistry. The results show that isoprenaline and terbutaline-induced relaxation was lower in the aortas of rats with BPV. Relaxation responses to other vasorelaxant compounds were similar in both groups of rats. Histological analysis revealed a lower level of ß2-adrenoceptor and confocal microscopy showed minor cytosolic Ca(2+) concentration in endothelial cells stimulated by the ß2-adrenoceptor agonist in rats with BPV. In conclusion, BPV leads to desensitization of the ß2-adrenoceptor, which could contribute to worse ß-adrenoceptor agonist-induced relaxation in isolated aortas.

Effects of microgravity elicited by parabolic flight on abdominal aortic pressure and heart rate in rats.

Abdominal aortic pressure (AAP), heart rate (HR), and aortic nerve activity (ANA) during parabolic flight were measured by using a telemetry system to clarify the acute effect of microgravity (microG) on hemodynamics in rats. While the animals were conscious, AAP increased up to 119 +/- 3 mmHg on exposure to microG compared with the value at 1 G (95 +/- 3 mmHg; P < 0.001), whereas AAP decreased immediately on exposure to microG under urethane anesthesia (microG: 72 +/- 9 mmHg vs. 1 G: 78 +/- 8 mmHg; P < 0.05). HR also increased during microG in conscious animals (microG: 349 +/- 12 beats/min vs. 1 G: 324+9 beats/min; P < 0.01), although no change was observed under anesthesia. ANA, which was measured under anesthesia, decreased in response to acute microG exposure (microG: 33 +/- 7 counts/s vs. 1 G: 49 +/- 5 counts/s; P < 0.01). These results suggest that microG essentially induces a decrease of arterial pressure; however, emotional stress and body movements affect the responses of arterial pressure and HR during exposure to acute microG.

Compensatory vasoconstrictor effects of sodium pentobarbital on the hindquarters of conscious normotensive control and lumbar-sympathectomized Wistar rats.

The aim of this study was to compare the vasoconstrictor effect of sodium pentobarbital on the hindquarter resistance of intact control Wistar rats with the effect on lumbar-sympathectomized rats. For this purpose, mean arterial pressure (MAP) and hindquarter (supplied terminal aorta) flow (HQF) were simultaneously measured in these conscious rats with an arterial in dwelling cannula and electromagnetic flow probe implanted around the terminal aorta. Hindquarter resistance (HQR) was calculated as MAP divided by HQF. In the intact control conscious rats, subsequent pentobarbital anesthesia (30 mg/kg, i.v.) caused an increase in HQR (+43.5 +/- 7.4%, mean +/- S.E.M.) and a decrease in MAP (-17.0 +/- 3.2%). After pentobarbital anesthesia, subsequent ganglionic blockade with hexamethonium bromide (C6; 25 mg, i.v.) induced a significant decrease in HQR (-30.9 +/- 3.0%) with a further lowering of MAP (-20.9 +/- 1.6%). However, in rats not anesthetized with sodium pentobarbital, C6 alone induced almost no change in HQR (-3.4 +/- 5.3%), even when MAP was lowered (-24.2 +/- 2.5%). In the lumbar-sympathectomized rats, pentobarbital anesthesia produced almost no change in HQR (-11.7 +/- 4.4%), although MAP decreased significantly (-24.3 +/- 2.2%). These findings suggest that: (1) sodium pentobarbital anesthesia newly generates a compensatory vasoconstrictor tone in the hindquarters acting against the depressor effect, and (2) the vasocompensator tone is controlled by the efferent fibers, including those in the lumbar sympathetic nerves.

The cholinergic innervation of the aorta.

The cholinergic innervation of the aorta has been studied in some mammalian species. Cholinergic nerve fibers (CNF) are organized in the aorta of the rabbit, kid, lamb, and guinea pig in 2 plexuses. The plexuses of CNF consist of a superficial plexus localized in the adventitial layer and a deep one localized in the adventitial-medial transitional zone. Some CNF reach the outer layers of the media. In the aorta of the dog, mouse and rat CNF are organized in a single plexus localized in the adventitial layer. This nerve plexus is formed of CNF that for the most part are distributed to the vasa vasorum. The chemical sympathectomy don't alters the pattern of the cholinergic innervation of the aorta, indicating that stained CNF are parasympathetic in nature. The meaning of a cholinergic innervation of the aortic wall is discussed.

Adrenergic innervation of aortic patch-grafts in rats.

The regeneration of vascular adrenergic nerves was studied using the glyoxylic acid-induced fluorescence method for the specific demonstration of adrenergic nerves in syngeneic patch-grafts of the right atrium of the heart, vena cava and glutaraldehyde-treated vena cava transplanted into the abdominal aorta of the rat. Glutaraldehyde-treated segments of the supradiaphragmatic inferior vena cava were transplanted into the abdominal aorta of rats as well. At the end of the observation period of 24 weeks limited, patchy and defective innervation was observed in the syngeneic vena cava and atrial patches. No adrenergic nerves were found in the glutaraldehyde-treated vein patch-grafts or vein grafts. Owing to the very poor innervation of atrial and venous patch-grafts the results are not entirely in agreement with the target organ concept of adrenergic nerve regeneration. In this study the suture line around the patch graft probably hampers regeneration of vascular adrenergic nerves in the patches.

Afferent mechanism of renal sympathetic nerve activity shutdown induced by short period of microgravity.

NASA: The present study was designed to examine acute responses of renal sympathetic nerve activity in rats to a short period of microgravity. Free drops were performed in a 100 m drop tube. Responses of atrial pressure, heart rate, aortic flow velocity and renal sympathetic nerve activity are presented. Results indicate that renal sympathetic nerve activity was suppressed during microgravity. The response was transient.^ieng

[Erection disorders after implantation of aorto-bifemoral prosthesis]. / Zaburzenia erekcji po wszczepieniu protezy aortalno-dwuudowej.

In this paper we present sexual complications occurring after implantation of vascular aorto-bifemoral prosthesis. We have sent an inquiry to 1236 men, who were operated in Vascular Department of Medical Academy in Wroclaw in years 1983-1997. We received 659 answers. Additionally 302 patients were examined. We noticed disorders of erection after vascular operation in 350 cases. In 29 cases erection reappeared after operation. Only 112 patients declared correct ejaculation and 137 men have satisfied sexual life. This results present problem of postoperative ischaemia of minor pelvis and trauma to neural plexus of bifurcation of aorta. In cases of younger sexually active men, who need revascularisation of lower extremities by implantation of vascular aortobifemoral prosthesis we suggest endarterectomy of hypogastric artery and/or implantation this artery to prosthesis.

Increased stiffness and cell-matrix interactions of abdominal aorta in two experimental nonhypertensive models: long-term chemically sympathectomized and sinoaortic denervated rats.

RATIONALE: Sinoaortic denervated (SAD) and chemically sympathectomized (SNX) rats are characterized by a decrease in arterial distensibility without hypertension and would, thus, be relevant for analyzing arterial wall stiffening independently of blood pressure level. The fibronectin network, which plays a pivotal role in cell-matrix interactions, is a major determinant of arterial stiffness. We hypothesized that in SAD and SNX rats, arterial stiffness is increased, due to alterations of cell-matrix anchoring leading to spatial reorganization of the extracellular matrix. METHODS: The intrinsic elastic properties of the arterial wall were evaluated in vivo by the relationship between incremental elastic modulus determined by echotracking and circumferential wall stress. The changes of cell-extracellular matrix links in the abdominal aorta were evaluated by studying fibronectin, vascular integrin receptors, and ultrastructural features of the aorta by immunochemistry. RESULTS: In both experimental conditions, wall stiffness increased, associated with different modifications of cell-extracellular matrix adhesion. In SAD rats, increased media cross-sectional area was coupled with an increase of muscle cell attachments to its extracellular matrix via fibronectin and its α5-ß1 integrin. In SNX rats, reduced media cross-sectional area was associated with upregulation of αv-ß3 integrin and more extensive connections between dense bands and elastic fibers despite the disruption of the elastic lamellae. CONCLUSION: In aorta of SNX and SAD rats, a similar arterial stiffness is associated to different structural alterations. An increase in αvß3 or α5ß1 integrins together with the already reported increase in the proportion of less distensible (collagen) to more distensible (elastin) components in both models contributes to remodeling and stiffening of the abdominal aorta.

Influence of antagonist sensory and sympathetic nerves on smooth muscle cell differentiation in hypercholesterolemic rat.

The effect of sympathectomy and sensory denervation on vascular smooth muscle cell (SMC) differentiation was investigated in hypercholesterolemic rats. Newborn rats received injections of guanethidine, capsaicin or both for denervations. Shams received injections of vehicles. The four groups were fed 1% cholesterol diet for 3 months. Intact normocholesterolemic rats were also exploited. Serum total cholesterol and systolic blood pressure (SBP) were measured. Lipid presence in the arterial wall was shown by Red-Oil-O staining. Catecholamine- and CGRP-containing fibres, vimentin and the adult SMC markers alpha-SMC-actin, desmin and h-caldesmon were analysed in abdominal aorta by western blot and confocal microscope. The sympathetic (catecholamine) fibres and SBP increased after sensory denervation while the sensory (CGRP) fibres increased and SBP decreased after sympathectomy. SBP was not changed after double denervation. Total cholesterol increased in sham and rose further after sympathectomy. Vimentin and the three adult SMC markers were not influenced by hypercholesterolemia. However, in the sympathectomized aorta, vimentin increased, desmin did not change, whereas alpha-SMC-actin and h-caldesmon decreased. In the sensory-denervated aorta, vimentin decreased, desmin increased, alpha-SMC-actin did not change and h-caldesmon decreased but less than in sympathectomized aorta. In the doubly denervated aorta, vimentin did not change and the three adult SMC markers decreased, although less than in sympathectomized aorta for alpha-SMC-actin and h-caldesmon. Thickened intima was identified by Red-Oil-O staining in the sympathectomized and (less remarkably) doubly denervated aortas containing SMCs not fully dedifferentiated. Our findings suggest that sympathectomy induces intimal thickening and favours SMC dedifferentiation, whereas sensory denervation favours SMC differentiation.