Investigations of the Function of the Vascular Endothelium in Portal Hypertensive Rats

Cawley, Teresa; Breslin, Elaine; Geraghty, James; Osborne, Henry; Docherty, James R.

doi:10.1159/000139350

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…The increased contractile responsiveness of the aorta found in this study, and of the mesenteric artery in our previous study [12,13], contrasts with reports of decreased responsiveness of the in situ mesenteric vascular bed of pre-hepatic portal hypertensive rats or cirrhotic rats to vasoconstrictors such as noradrenaline, endothelin-1 and angiotensin II [7][8][9]17,18]. Pressor responses to angiotensin II also decreased in bile duct-ligated dogs [19].…”

Section: Strain Days Agonistcontrasting

confidence: 99%

“…We have previously reported that the maximum contractile responses to noradrenaline, KCl and the thromboxane mimetic U46199 are significantly increased in mesenteric arteries from portal hypertensive Wistar rats compared with sham-operated animals [12,13]. In comparison, many of the above mentioned studies of portal hypertension employed the Sprague-Dawley rat and examined aortic rings.…”

Section: Introductionmentioning

confidence: 99%

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Portal hypertension increases vasoconstrictor responsiveness of rat aorta

CONNOLLY¹,

CAWLEY²,

MCCORMICK³

et al. 1999

Clinical Science

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We have examined the effects of pre-hepatic portal hypertension on the responsiveness of aorta from Wistar and Sprague-Dawley rats. Rats were made portal hypertensive by creating a calibrated portal vein stenosis, or sham operated. In rat aorta, there was no significant difference between portal hypertensive and sham-operated animals in the contractile potency of KCl, noradrenaline or phenylephrine. In aortas from Wistar rats, the maximum response to KCl (0.71+/-0.12 g) and noradrenaline (1.00+/-0.17 g) but not phenylephrine (0.86+/-0.10 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.45+/-0.04 g, 0.57+/-0.07 g, 0.71+/-0.05 g respectively). In aortas from Sprague-Dawley rats, the maximum response to KCl (1. 21+/-0.21 g) and phenylephrine (1.54+/-0.30 g) but not noradrenaline (0.93+/-0.09 g) in portal hypertensive animals was significantly increased compared with that in sham-operated animals (0.59+/-0.09 g, 0.76+/-0.11 g, 1.04+/-0.10 g respectively). There was no difference between portal hypertensive and sham-operated Wistar rats in the affinity or maximum number of binding sites for [3H]prazosin to alpha1-adrenoceptors in cardiac ventricular membranes. It is concluded that portal hypertension tends to produce an increase rather than a decrease in the contractile response to vasoconstrictors in aorta from both Wistar and Sprague-Dawley rats. This suggests that the diminished responsiveness to vasoconstrictors reported in portal hypertensive rats in vivo is not due to a diminished responsiveness at the level of the vascular smooth muscle.

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Section: Strain Days Agonistcontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Portal hypertension increases vasoconstrictor responsiveness of rat aorta

CONNOLLY¹,

CAWLEY²,

MCCORMICK³

et al. 1999

Clinical Science

Self Cite

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“…Seven days after portal vein ligation, shunting was 66.5±14.3% ( n = 3). This result correlated well with values for degree of shunting obtained 7 days post ligation by Cawley et al (1995b).…”

Section: Resultssupporting

confidence: 85%

“…In this study we confirmed that our animals were portal hypertensive by examining, with the radioactive microsphere techique, the degree of shunting. Porto‐systemic shunting is effectively nil up to 3 days post portal vein ligation, but is near maximum 7 days post ligation (Cawley et al , 1995b). At seven days post ligation we showed that there was 66.5±14.3% porto‐systemic shunting, similar to values obtained by Cawley et al (1995b).…”

Section: Discussionmentioning

confidence: 99%

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Vascular actions of octreotide in the portal hypertensive rat

Aboud

Connolly

McCormick

et al. 1997

British J Pharmacology

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1 We have investigated the actions of the somatostatin analogue octreotide in the portal hypertensive Wistar rat in vivo and in rat small mesenteric artery and aorta in vitro. 2 In small mesenteric artery, octreotide (0.1 ± 0.3 mM) failed to produce any direct contraction, nor did it aect contractions to noradrenaline (NA, 10 mM) or endothelium-dependent relaxations to acetylcholine. 3 In rat aorta, octreotide (0.3 mM) and somatostatin (1 mM) failed to aect contractions to NA (1 mM), or concentration-contractile response curves to NA. 4 In rat vas deferens, octreotide and somatostatin signi®cantly reduced contractile responses to electrical stimulation with pD 2 values (7log IC 50 ) of 8.19+0.10 (n=4) and 8.16+0.26 (n=4), respectively. Hence, the lack of eect of these agents in aorta or mesenteric artery was not due to lack of ecacy or inappropriate choice of concentration. 5 In the anaesthetized portal hypertensive rat, intravenous injection of octreotide (1 ± 100 mg kg 71 ) did not signi®cantly aect systemic blood pressure, nor did it aect mesenteric vascular conductance as measured by laser doppler¯ow probes. However, octreotide (100 mg kg 71) signi®cantly reduced vascular conductance to 74.2+7.7% of control (n=6) in porto-systemic shunt vessels as measured by laser doppler¯ow probes. 6 Phenylephrine (1 mg kg 71 ) signi®cantly raised blood pressure and signi®cantly decreased vascular conductance in both mesenteric (66.6+3.7% of control) and porto-systemic shunt vessels (58.7+10.0% of control). 7 It was concluded that octreotide has selective eects on porto-systemic shunt vessles in vivo in the portal hypertensive rat.

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Comparison of the effects of nitric oxide synthase inhibition and guanylate cyclase inhibition on vascular contraction in vitro and in vivo in the rat

Abdullah

Cawley

Connolly

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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We have investigated the differences between the nitric oxide synthase inhibitor (NOSI), L-NMMA, and the guanylate cyclase inhibitors (GCI), methylene blue and LY 83583, in their abilities to increase vasoconstrictor responses in vitro and in vivo. In rat small mesenteric arterial rings, 1 h exposure to the NOSI, L-NMMA (100 microM), and the GCI, methylene blue (10 microM), alone or in combination with L-NMMA, caused a significant reduction in the maximum relaxation to ACh in mesenteric arteries pre-contracted with the thromboxane mimetic U46619 (10 microM). Hence, both NOSI and GCI inhibit endothelium-dependent relaxations to ACh in rat small mesenteric artery. However, 1 h exposure to L-NMMA and L-NNA (both 100 microM), but not methylene blue (10 microM), significantly increased the contractile response to U-46619 (10 microM) in rat small mesenteric artery. It was decided to investigate further this difference between NOSI and methylene blue. In rat small mesenteric arterial rings, L-NMMA (10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (10 microM), when administered during the contraction. However, methylene blue (1-10 microM) increased the contractile response to KCl but not noradrenaline. In rat aortic rings, L-NMMA (100 microM), methylene blue (1-10 microM) and LY 83583 (1-10 microM) significantly increased the contractile response to KCl (40 mM) or to noradrenaline (1 microM). In the pithed rat preparation, L-NMMA (40.3 micromol kg(-1), i.v.) significantly increased the pressor response both to bolus injection of noradrenaline (3.13 nmol kg[-1]) and to spinal pressor nerve stimulation. However, methylene blue (3.13-15.6 micromol kg[-1]) or LY 83583 (4.0-40.0 micromol kg[-1]), failed to affect pressor responses to either NA or pressor nerve stimulation. Hence, there are differences between NOSI and GCI in their abilities to increase vasoconstrictor responses, especially when comparing responses in vitro and in vivo. This suggests that nitric oxide has actions in addition to activation of guanylate cyclase to modulate vasoconstrictor responses, presumably by membrane hyperpolarisation, and that this action may be more important in vivo.

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Investigations of the Function of the Vascular Endothelium in Portal Hypertensive Rats

Cited by 10 publications

References 23 publications

Portal hypertension increases vasoconstrictor responsiveness of rat aorta

Portal hypertension increases vasoconstrictor responsiveness of rat aorta

Vascular actions of octreotide in the portal hypertensive rat

Comparison of the effects of nitric oxide synthase inhibition and guanylate cyclase inhibition on vascular contraction in vitro and in vivo in the rat

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