Endothelium‐dependent Relaxation of Canine Uterine Artery in Response to Acetylcholine: the Possible Involvement of Alternative Pathways

Pesic, Srdjan; Grbović, Leposava; Jovanović, Aleksandar; Radenković, Miroslav; Stojić, Dragica Lj.; Cvetković, Zorica; Ilić, Ivan

doi:10.1046/j.1439-0442.2003.00568.x

Cited by 4 publications

(3 citation statements)

References 38 publications

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“…This finding is in agreement with the studies of other authors (Matsumoto et al. , 1987, 1992) as well as with our previous report (Pesic et al. , 2003) where we suggested NO involvement in this acetylcholine‐induced effect.…”

Section: Discussionsupporting

confidence: 94%

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Pesic

Grbović

Stoiljković

et al. 2009

Vet Pharm & Therapeutics

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Acetylcholine interacts with endothelial muscarinic receptors releasing nitric oxide and causing vasodilatation. To identify the receptor subtype responsible for acetylcholine-induced relaxation in canine uterine artery, the usual organ bath method for in vitro investigation on isolated blood vessels was applied. Using a range of muscarinic receptor antagonists such as atropine (nonselective), pirenzepine (M(1)-selective), methoctramine (M(2)-selective) and p-fluoro-hexahydro-sila-difenidol (p-FHHSiD) (M(1)/M(3)) and determining pA2 value of those antagonists through Shild analysis, we aimed at establishing a precise receptor mechanism underlying acetylcholine-induced relaxation in isolated canine uterine artery. The relaxation of uterine arterial rings in response to acetylcholine in the presence or absence of selective muscarinic receptors antagonists was calculated using concentration response curves. Acetylcholine induced concentration-dependent and endothelium-dependent relaxation of arterial rings precontracted with phenylephrine (pEC(50) = 6.90 +/- 0.02). Muscarinic receptors antagonists atropine, pirenzepine, methoctramine and p-FHHSiD competitively antagonized the response to acetylcholine and obtained pA(2) values were 9.91 +/- 0.06, 6.60 +/- 0.04, 6.21 +/- 0.08 and 8.05 +/- 0.1, respectively. This study showed that acetylcholine induced endothelium-dependent relaxation of canine uterine artery by stimulation of muscarinic receptors localized on the endothelial cells. On the basis of differential antagonist affinity, we suggest that the muscarinic receptors involved in the acetylcholine-induced relaxation of canine uterine artery are predominantly of M(3) subtype.

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Section: Discussionsupporting

confidence: 94%

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Pesic

Grbović

Stoiljković

et al. 2009

Vet Pharm & Therapeutics

Self Cite

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“…Immunoreactive tenocytes are observed in a but not in b. TRITC staining. Bars 25 μm presumably being mediated by the endothelial production of nitric oxide (Pesic et al 2003). In accordance with several previous reports describing the location of muscarinic ACh receptors in blood vessel walls in other tissues (e.g., Badaut et al 1997), we have found M 2 R immunoreactivity to be mainly localized to the endothelial part of the vessels.…”

Section: Presence Of M 2 Immunoreactivity In Cells In Blood Vessel Wasupporting

confidence: 92%

Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)

et al. 2007

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Limited information is available concerning the existence of a cholinergic system in the human Achilles tendon. We have studied pain-free normal Achilles tendons and chronically painful Achilles tendinosis tendons with regard to immunohistochemical expression patterns of the M(2) muscarinic acetylcholine receptor (M(2)R), choline acetyltransferase (ChAT), and vesicular acetylcholine transporter (VAChT). M(2)R immunoreactivity was detected in the walls of blood vessels. As evidenced via parallel staining for CD31 and alpha-smooth muscle actin, most M(2)R immunoreactivity was present in the endothelium. M(2)R immunoreactivity also occured in tenocytes, which regularly immunoreact for vimentin. The degree of M(2)R immunoreactivity was highly variable, tendinosis tendons that exhibit hypercellularity and hypervascularity showing the highest levels of immunostaining. Immunoreaction for ChAT and VAChT was detected in tenocytes in tendinosis specimens, particularly in aberrant cells. In situ hybridization revealed that mRNA for ChAT is present in tenocytes in tendinosis specimens. Our results suggest that autocrine/paracrine effects occur concerning the tenocytes in tendinosis. Up-regulation/down-regulation in the levels of M(2)R immunoreactivity possibly take place in tenocytes and blood vessel cells during the various stages of tendinosis. The presumed local production of acetylcholine (ACh), as evidenced by immunoreactivity for ChAT and VAChT and the detection of ChAT mRNA, appears to evolve in response to tendinosis. These observations are of importance because of the well-known vasoactive, trophic, and pain-modulating effects that ACh is known to have and do unexpectedly establish the presence of a non-neuronal cholinergic system in the Achilles tendon.

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“…In vitro canine experiments have demonstrated the importance of prostaglandins in regulating uterine vascular tone 37 . Additionally, in dogs, acetylcholine‐induced uterine artery vasodilatation probably occurs through the release of endothelium‐derived relaxing factors, such as nitric oxide, endothelium‐derived hyperpolarizing factor, and prostacyclin 38–40 . These vasodilator molecular pathways may contribute to explaining the RI and PI values found at the end of the study.…”

Section: Discussionmentioning

confidence: 89%

Doppler ultrasonographic evaluation of medically treated female dogs with cystic endometrial hyperplasia–pyometra complex

Batista

Gobello

Rube

et al. 2022

Vet Radiology Ultrasound

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Monitoring the treatment outcome of canine cystic endometrial hyperplasia-pyometra complex (CEH-P) is essential to identify nonresponding patients who might require a rapid intervention to avoid life-threatening conditions. Uterine artery Doppler characterization may contribute to monitoring medically treated CEH-P, but published studies are currently lacking. Therefore, the aim of this longitudinal prospective observational study was to evaluate uterine artery resistance changes in the medical treatment of female dogs with CEH-P. Twelve diestrous female dogs suffering from CEH-P were treated with a combined protocol of cabergoline, cloprostenol, and antibiotics. The animals were clinically and ultrasonographically evaluated before the beginning of treatment (day 0) and on days 3, 7, 14, 21, and 28. The widest transverse diameter and luminal diameter of uterine horns were measured, as well as the peak systolic velocity (PSV) and end diastolic velocity (EDV) of uterine arteries. The resistance index (RI), pulsatility index (PI), and notch deep index (NDI) were calculated. On day 3, nine of 12 animals showed clinical improvement. In all these female dogs, the widest transverse sectional diameter (P < 0.01), luminal diameter (P < 0.01), PSV (P < 0.01), and EDV (P < 0.01) progressively decreased, while RI (P < 0.01), PI (P < 0.01), and NDI (P < 0.01) increased up to day 21. In nonresponding dogs (3/12), Doppler parameters remained unchanged. Although comparisons of PSV, EDV, and NDI were significantly different, these results should be cautiously interpreted due to the low statistical power. female dogs that responded to this treatment showed an increase in uterine artery resistance, along with clinical and ultrasonographic improvement.

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Endothelium‐dependent Relaxation of Canine Uterine Artery in Response to Acetylcholine: the Possible Involvement of Alternative Pathways

Cited by 4 publications

References 38 publications

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Functional characterization of the muscarinic receptors involved in endothelium‐dependent relaxation in isolated canine uterine artery

Presence of a non-neuronal cholinergic system and occurrence of up- and down-regulation in expression of M2 muscarinic acetylcholine receptors: new aspects of importance regarding Achilles tendon tendinosis (tendinopathy)

Doppler ultrasonographic evaluation of medically treated female dogs with cystic endometrial hyperplasia–pyometra complex

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