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Aims: High fructose levels are found in diabetes mellitus, associated with high corn syrup diets, and have been claimed to cause hypertension. As the direct effects on conduit and resistance arteries have not been previously reported, we measured these in vivo in the anaesthetized pig with instrumented iliac arteries., Methods: Experiments were performed on the iliac artery preparation in the anaesthetized pig: blood flow, diameter and pressure were measured in the iliac., Results: The change in diameter of an occluded iliac artery segment filled with hyperfructosemic (15 μm) blood was 89.5 ± 22.1 μm (mean ± SE), contrasted with 7.7 ± 13.06 μm control (P = 0.005, paired t-test, n = 6). There was no significant difference when compared with blood containing both hyperfructosemic blood and the nitric oxide synthesis inhibitor, N(G)-nitro-l-arginine methyl ester (250 μg mL(-1)). Step changes in pressure and flow were achieved by progressive arterial stenosis during control saline and 15 μm min(-1) fructose downstream intra-arterial infusions. Linear regression of the step changes in blood pressure versus the instantaneous step changes in blood flow showed a statistically significant decrease in slope of the conductance (P < 0.001, analysis of covariance), indicating an increase in instantaneous peripheral vascular resistance. Peripheral autoregulation and conduit artery shear-stress-mediated dilatation were not significantly altered., Conclusion: An elevated level of fructose caused dilatation of a conduit artery but constriction of resistance vessels. The latter effect could account, if maintained long-term, for the hypertension claimed to be due to hyperfuctosemia., (© 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.)

1. The effects of changes in mean and pulsatile shear stress on the diameter of the iliac of the anaesthetized pig were investigated in the presence of clazosentan and tezosentan. 2. A total of 17 pigs were used. Mean shear stress was increased by infusing acetylcholine downstream (2-20 μg/min) through the deep femoral artery. Pulsatile shear stress was enhanced first by injecting varying volumes (1-10 mL) of calcium gluconate (stock 10 mg/mL) directly into the left ventricle. Second, by electrical stimulation of the left sympathetic nerves to the heart (1-16 Hz, 4 min duration, supramaximal voltage). 3. An increase in mean shear stress induced a vasodilation that was not altered significantly by the selective endothelin A antagonist clazosentan (10 mg/kg i.v.). Similarly, the vasoconstriction induced by an increase in pulsatile shear stress brought about by either calcium gluconate injections or left sympathetic nerve stimulation was unaffected by clazosentan. However, tezosentan (10 mg/kg i.v.), significantly attenuated the vasoconstriction induced by an increase in pulsatile shear stress. 4. In conclusion, an increase in pulsatile shear stress causes vasoconstriction of the pig iliac artery, which is attenuated by dual endothelin receptor antagonism, but not by specific endothelin A blockade., (© 2011 The Authors. Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.)

Aim: We tested the hypothesis that dilatation of a feeding artery may be elicited by transmission of a signal through the tissue of the arterial wall from a vasodilated peripheral vascular bed., Methods: In eight pentobarbital anaesthetized pigs, acetylcholine (ACh, an endothelium-dependent vasodilator) was injected intra-arterially above (upstream) and below (downstream) a test segment of the left iliac artery, the diameter of which was measured continuously by sonomicrometry., Results: Under control conditions, ACh injections upstream and downstream of the test segment caused dilatation. Downstream injection dilated the peripheral arterioles, resulting in increased blood flow and proximal dilatation. This is a shear stress, nitric oxide (NO)-dependent response. The experiment was then repeated after applying a stenosis to prevent the increased flow caused by downstream injection of ACh; the stenosis was placed either above the site of diameter measurement to allow retrograde conduction, or below that site to prevent distally injected ACh reaching the measurement site. Under these conditions, downstream injection of ACh had a minimal effect on the shear stress of the test segment with no increase in test segment diameter. This was not due to endothelial damage or dysfunction as injection of ACh upstream still caused a large increase in test segment diameter., Conclusions: Our results indicate that dilatation of the feeding artery of a vasodilated bed is caused by increased shear stress within the feeding artery and not via a signal transmitted through the arterial wall from below.

Comparisons were made between responses evoked by noradrenaline (NA) in iliac artery rings from normoxic (N) rats and chronically hypoxic (CH) rats kept in 12 % O(2) for 3-4 weeks. At P(O(2)) of 100 mmHg, cumulative concentration-response curves (CCRC) to NA were greatly depressed in endothelium-intact (E+) rings, but not endothelium-denuded (E-) rings, of CH rats relative to N rats. However, CCRCs evoked by NA in E+ and E- rings during nitric oxide (NO) synthase inhibition were similar in N and CH rats. Reducing P(O(2)) to 55 mmHg depressed CCRCs to NA in E+ and E- rings of CH and N rats in the absence and presence of NO synthase inhibition. At P(O(2)) of 100 mmHg, CCRCs evoked by phenylephrine were comparable in E+ and E- rings of N and CH rats as were CCRCs for the relaxation evoked by isoprenaline, which were similarly rightward shifted by NO synthase inhibition. However, CCRCs evoked by the NO donor sodium nitroprusside were leftward shifted in E- rings of CH rats relative to N rats. Further, in the presence of the alpha(2) adrenoceptor inhibitor rauwolscine, CCRCs to NA were comparable in E+ rings of CH and N rats. Thus, the depressive effects of chronic hypoxia on NA-evoked contractions of iliac artery are additional to those of acute hypoxia. We propose that they reflect a facilitation of the contribution of NO to alpha(2) adrenoceptor-evoked relaxation that includes an increased sensitivity of the vascular smooth muscle of arteries from CH rats to NO.

Gastric distension in anaesthetized pigs reflexly elicits peripheral vasoconstriction and an increase in plasma renin activity (PRA), with vagal afferent and sympathetic efferent limbs. The aim of the present study was to quantify the contribution of the renin-angiotensin system to the peripheral vasoconstriction. In pigs anaesthetized with alpha-chloralose, changes in anterior descending coronary, superior mesenteric and left external iliac blood flow caused by stomach distension before and after blockade of angiotensin II receptors with losartan were assessed using electromagnetic flowmeters. Gastric distension for periods of 30 min was performed by injecting 0.8 l warm Ringer solution into balloons positioned within the viscus. Changes in heart rate and renal blood flow were prevented by atrial pacing and injection of phentolamine into the renal arteries, and changes in regional perfusion pressure and in baroreceptor activity were minimized by aortic constriction and denervation of the carotid sinuses. PRA was assessed by radioimmunoassay of angiotensin I. Before blockade of angiotensin II receptors by administration of losartan, stomach distension decreased coronary blood flow by 14.2 % in six pigs and mesenteric and iliac blood flow by 11 % and 17.3 %, respectively, in another six pigs. After administration of losartan, these decreases were significantly reduced to 7.4 %, 6.8 % and 8.7 %, respectively. The above responses were abolished by bilateral section of the subdiaphragmatic vagal nerves. These results show that the peripheral vasoconstriction reflexly caused by stomach distension was significantly contributed to by the concomitant activation of the renin-angiotensin system.

In rings of rat iliac artery, contractions were evoked by noradrenaline (NA), the selective alpha(1) adrenoceptor agonist phenylephrine (PE), and K(+), which causes depolarisation-induced contraction. There was no evidence of alpha(2) adrenoceptor-evoked contraction. Hypoxia, induced by reducing P(O(2)) in the bath from 100 mmHg to 70, 55 or 40 mmHg, had similar effects on rings with (E+) and without (E-) endothelium. In E- rings, the NA concentration-response curve was biphasic, whereas that for PE was monophasic. Hypoxia reduced maximum contractions in response to NA and PE (NA(max) and PE(max), respectively) without affecting the concentrations that evoked 50 % of maximum contraction (EC(50)). At P(O(2)) of 70 mmHg, NA(max) of the high affinity alpha(1) receptor for NA (NA(maxh)) and PE(max) were reduced by approximately 15 %, but at P(O(2)) of 55 and 40 mmHg, NA(maxh) was severely attenuated while PE(max) fell by 45 and 75 %, respectively. Similarly, the Ca(2+) channel blocker nicardipine depressed NA(maxh) and PE(max), but P(O(2)) of 55 mmHg further reduced NA(max) and PE(max). Hypoxia also reduced contractions evoked by NA, PE or K(+) at the concentrations required to produce 80 % of the maximum contraction (EC(80)), receptor-mediated contractions being more affected. Ca(2+)-free conditions reduced the contractions evoked by NA and PE, at the EC(80), to approximately 10 % of control. The K(+) channel inhibitors glibenclamide and tetraethylammonium did not prevent hypoxia-induced depression of PE-evoked contraction. Thus, contractions evoked in iliac artery by the high affinity subtype of alpha(1) adrenoceptor for NA, which may respond to circulating levels of NA, and by the single alpha(1) adrenoceptor subtype for PE, are especially vulnerable to P(O(2)) levels less-than-or-equal 55 mmHg. We propose that this reflects hypoxia-induced inhibition of Ca(2+) influx through L-type and receptor-operated Ca(2+) channels; K(+) channel opening makes little contribution.

The present study was undertaken in anaesthetized pigs to determine the primary reflex effects of gastric distension on the peripheral circulation. Changes in blood flow in the splenic, superior mesenteric, left renal and left external iliac arteries were assessed using electromagnetic flowmeters during distension of a balloon in the stomach, performed at constant aortic blood pressure and heart rate, with 0.6 l of Ringer solution (mean gastric transmural pressure of about 12 mmHg). In fourteen pigs, a decrease in splenic, renal and iliac flows and variable changes in mesenteric flow were obtained. A decrease in mesenteric flow and more marked decreases in the other flows occurred in response to the distension after the administration of propranolol or butoxamine. In five pigs, the vasoconstrictive responses were graded by step increments in gastric distending volume from 0.4 to 0.8 l. The above responses were abolished by the administration of phentolamine (eight pigs) and by bilateral cervical vagotomy (six pigs). The results showed that innocuous distension of the stomach in anaesthetized pigs reflexly caused vasoconstriction in the splenic, renal and iliac vascular beds; vasoconstriction also occurred in the mesenteric vascular bed but only after beta-blockade. These reflex responses were mediated by sympathetic mechanisms which involved both alpha and beta vascular adrenoceptors and their afferent limb was in the vagal nerves.

The quantitative relationship between, increase in blood flow and arterial diameter was determined in an anaesthetized dog preparation (pentobarbitone, induction 30 mg kg-1 i.v., maintenance 3 mg kg-1 i.v. every 30 min). Changes in external iliac artery diameter were measured using piezoelectric ultrasound transducers capable of measuring diameters within the range of 2-20 mm with a resolution of +/- 0.005 mm. The diameter of the artery was measured at two sites, at one of which the endothelium was damaged using a balloon angioplasty catheter. Increases in blood flow were brought about by a combination of vasodilatation and cardiac stimulation (intra-arterial administration of acetylcholine, downstream to the sites of diameter measurement, and electrical stimulation of the left ansa subclavia), thereby preventing large changes in blood pressure. The effects of both transient and maintained increases in blood flow on mean arterial diameter in the section of artery with intact endothelium were measured. Transient increases in mean flow from 147 +/- 0.21 to 611 +/- 80.0 ml min-1 caused increases in diameter of 0.12 +/- 0.02 mm from a control of 5.42 +/- 0.19 mm. The mean delay between maximum flow and maximum diameter was 24.51 +/- 1.1 s and the half-time for the return to control diameter was 82.0 +/- 9.6 s, compared with 12.1 +/- 1.5 s for the return to control flow. Maintained (3-4 min) increases in mean blood flow (from 104.7 +/- 15.1 to 694.7 +/- 135.1 ml min-1) produced larger increases in diameter of 0.48 +/- 0.30 mm from a control diameter of 4.89 +/- 0.12 mm. These changes in diameter were abolished by N omega-nitro-L-arginine methyl ester (L-NAME. 10-100 mg kg-1 i.v.). In the section of artery with damaged endothelium, changes in diameter were relatively small and associated with small changes in blood pressure. This effect of a nearly 7-fold increase in flow on arterial diameter is dependent upon the integrity of the endothelium and the release of endothelium-derived relaxing factor and causes a 29% reduction in calculated boundary wall shear stress.

A biomimetic prosthesis was prepared from canine arterial wall by extraction with 70% formic acid. Under these conditions, the arterial architecture consisting of elastic lamella was conserved and the tensile strength was retained. Attachment of 51Cr-endothelial cells to the surface of the prosthesis was enhanced in the presence of collagen (50 micrograms/ml), fibronectin (20 micrograms/ml), and fibrinogen (500 micrograms/ml). These agents also enhanced the adhesion of 51Cr-platelets. However, preattachment of endothelial cells to prostheses prevented platelet adhesion.

Nineteen patients undergoing abdominal aortic aneurysm surgery were randomly assigned to two groups and investigated to elucidate the mechanisms of declamping hypotension. The control group of nine patients was kept at an average mean pulmonary artery occlusion pressure (MPAOP) of 11 mmHg (1.46 kPa) before declamping. The other group was volume loaded to a MPAOP of 16 mmHg (2.13 kPa) shortly before declamping. Following declamping there was a significantly greater decrease in mean arterial pressure in the control group, with the same reduction of MPAOP in both groups. In parallel, cardiac and stroke volume indices decreased in the control patients, but remained unchanged in the volume-loaded patients. In the control group there was a reduction in myocardial substrate utilization which was not seen in the volume-loaded patients. No signs of myocardial ischemia could be demonstrated in any of the groups. The results indicate that mismatching between intravascular volume and blood volume is the main cause of infrarenal aortic or common iliac artery declamping hypotension. Volume loading before declamping to a slightly elevated MPAOP can effectively prevent hypotension, while a normal MPAOP does not guarantee a stable hemodynamic situation after declamping.