Regional heterogeneity in EDHF‐mediated relaxation in the rat mesenteric vascular bed: role of small‐ and intermediate conductance calcium‐activated K+ channels

The mechanism of action of lithium, an effective treatment for bipolar disease, is still unknown. In this study, the mesenteric vascular beds of control rats and rats that were chronically treated with lithium were prepared by the McGregor method, and the mesenteric vascular bed vasorelaxation responses were examined. NADPH-diaphorase histochemistry was used to determine the activity of NOS (nitric oxide synthase) in mesenteric vascular beds. We demonstrated that ACh-induced vasorelaxation increased in the mesenteric vascular bed of rats treated with lithium. Acute Nο-nitro-l-arginine methyl ester (l-NAME) administration in the medium blocked ACh-induced vasorelaxation in the control group more effectively than in lithium-treated rats, while the vasorelaxant response to sodium nitroprusside, a NO donor, was not different between lithium-treated and control groups. Acute aminoguanidine administration blocked ACh-induced vasorelaxation of lithium-treated rats, but had no effect in the control rats. Furthermore, NOS activity, determined by NADPH-diaphorase staining, was significantly greater in the mesenteric vascular beds from chronic lithium-treated rats than in those from control rats. These data suggest that the enhanced ACh-induced endothelium-derived vasorelaxation in rat mesenteric bed from chronic lithium-treated rats might be associated with increased NOS activity, likely via iNOS. Simultaneous acute l-NAME and indomethacin administration suggests the possible upregulation of EDHF (endothelium-derived hyperpolarizing factor) in lithium-treated rats.

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α2-Adrenoceptor subsensitivity in mesenteric vascular bed of cholestatic rats: The role of nitric oxide and endogenous opioids

European Journal of Pharmacology ◽

10.1016/j.ejphar.2005.03.015 ◽

2005 ◽

Vol 514 (2-3) ◽

pp. 183-189 ◽

Cited By ~ 7

Author(s):

Amir Ali Borhani ◽

Golbahar Houshmand ◽

Morteza Samini ◽

Khodadad Namiranian ◽

Amir Reza Hajrasouliha ◽

...

Keyword(s):

Nitric Oxide ◽

Endogenous Opioids ◽

Vascular Bed ◽

Α2 Adrenoceptor ◽

Mesenteric Vascular Bed

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Endothelial COX-1 and -2 differentially affect reactivity of MVB in portal hypertensive rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00391.2001 ◽

2002 ◽

Vol 283 (3) ◽

pp. G587-G594 ◽

Cited By ~ 24

Author(s):

M. A. Potenza ◽

O. A. Botrugno ◽

M. A. De Salvia ◽

G. Lerro ◽

C. Nacci ◽

...

Keyword(s):

Portal Hypertension ◽

Hypertensive Rats ◽

Mesenteric Blood Flow ◽

Western Blots ◽

Vascular Bed ◽

Cox Inhibitor ◽

Mesenteric Vascular Bed ◽

Cox 2 ◽

Cox 1

Expression of constitutive and inducible cyclooxygenase (COX-1 and COX-2, respectively) and the role of prostanoids were investigated in the aorta and mesenteric vascular bed (MVB) from the portal vein-ligated rat (PVL) as a model of portal hypertension. Functional experiments were carried out in MVB from PVL and sham-operated rats in the absence or presence of the nonselective COX inhibitor indomethacin or the selective inhibitors of COX-1 (SC-560) or COX-2 (NS-398). Western blots of COX-1 and COX-2 proteins were evaluated in aorta and MVB, and PGI2 production by enzyme immunoassay of 6-keto-PGF1α was evaluated in the aorta. In the presence of functional endothelium, decreased contraction to norepinephrine (NE) and increased vasodilatation to ACh were observed in MVB from PVL. Exposure of MVB to indomethacin, SC-560, or NS-398 reversed the hyporeactivity to NE and the increased endothelial vasodilatation to ACh in PVL, with NS-398 being more potent than the other two inhibitors. Upregulation of COX-1 and COX-2 expressions was detected in aorta and MVB from PVL portal hypertensive rats, and increased production of 6-keto-PGF1α was observed in aorta from portal hypertensive rats. These results suggest that generation of endothelial vasodilator prostanoids, from COX-1 and COX-2 isoforms, accounts for the increased mesenteric blood flow in portal hypertension.

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The role of bradykinin, AT2 and angiotensin 1-7 receptors in the EDRF-dependent vasodilator effect of angiotensin II on the isolated mesenteric vascular bed of the rat

British Journal of Pharmacology ◽

10.1038/sj.bjp.0705669 ◽

2004 ◽

Vol 141 (5) ◽

pp. 860-866 ◽

Cited By ~ 33

Author(s):

R Soares De Moura ◽

A C Resende ◽

A F Emiliano ◽

T Tano ◽

A C Mendes-Ribeiro ◽

...

Keyword(s):

Angiotensin Ii ◽

Vasodilator Effect ◽

Vascular Bed ◽

Mesenteric Vascular Bed

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Regional heterogeneity in acetylcholine-induced relaxation in rat vascular bed: role of calcium-activated K+ channels

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.01383.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. H216-H222 ◽

Cited By ~ 52

Author(s):

Rob H. P. Hilgers ◽

Joseph Todd ◽

R. Clinton Webb

Keyword(s):

Mesenteric Artery ◽

Channel Blocker ◽

Inhibitory Effect ◽

Vasomotor Tone ◽

Response Curves ◽

Regional Heterogeneity ◽

Relative Contribution ◽

Vascular Bed ◽

Relative Mrna Expression

Ca+-activated K+-channels (KCa) regulate vasomotor tone via smooth muscle hyperpolarization and relaxation. The relative contribution of the endothelium-derived hyperpolarizing factor (EDHF)-mediated relaxation differs depending on vessel type and size. It is unknown whether these KCa channels are differentially distributed along the same vascular bed and hence have different roles in mediating the EDHF response. We therefore assessed the role of small- (SKCa), intermediate- (IKCa), and large-conductance (BKCa) channels in mediating acetylcholine-induced relaxations in both first- and fourth-order side branches of the rat superior mesenteric artery (MA1 and MA4, respectively). Two-millimeter segments of each MA were mounted in the wire myograph, incubated with Nω-nitro-l-arginine methyl ester (l-NAME, 100 μmol/l) and indomethacin (10 μmol/l), and precontracted with phenylephrine (10 μmol/l). Cumulative concentration-response curves to ACh (0.001–10 μmol/l) were performed in the absence or presence of selective KCa channel antagonists. Apamin almost completely abolished these relaxations in MA4 but only partially blocked relaxations in MA1. The selective IKCa channel blocker 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) caused a significantly greater inhibition of the ACh-induced relaxation in MA4 compared with MA1. Iberiotoxin had no inhibitory effect in MA4 but blunted relaxation in MA1. Relative mRNA expression levels of SKCa (rSK1, rSK3, and rSK4 = rIK1) were significantly higher in MA4 compared with MA1. BKCa (rBKα1 and rBKβ1) genes were similar in both MA1 and MA4. Our data demonstrate regional heterogeneity in SKCa and IKCa function and gene expression and stress the importance of these channels in smaller resistance-sized arteries, where the role of EDHF is more pronounced.

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Role of nitric oxyde in modulation of regionally different vascular responses in mesenteric vascular bed

Pathophysiology ◽

10.1016/0928-4680(94)90865-6 ◽

1994 ◽

Vol 1 ◽

pp. 426

Author(s):

L.A. Szirmai ◽

E. Monos ◽

W.J. Stekiel ◽

J.H. Lombard

Keyword(s):

Vascular Responses ◽

Vascular Bed ◽

Mesenteric Vascular Bed

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Analysis of the Effects of Candesartan in the Mesenteric Vascular Bed of the Cat

Hypertension ◽

10.1161/01.hyp.30.5.1260 ◽

1997 ◽

Vol 30 (5) ◽

pp. 1260-1266 ◽

Cited By ~ 10

Author(s):

Hunter C. Champion ◽

Philip J. Kadowitz

Keyword(s):

Vascular Bed ◽

Mesenteric Vascular Bed

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Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1995.269.3.h805 ◽

1995 ◽

Vol 269 (3) ◽

pp. H805-H811 ◽

Cited By ~ 16

Author(s):

S. Najibi ◽

R. A. Cohen

Keyword(s):

Carotid Artery ◽

Sodium Nitroprusside ◽

Channel Blocker ◽

Isometric Tension ◽

K Channel ◽

K Channels ◽

Rabbit Carotid Artery ◽

Cyclic Monophosphate ◽

Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

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