Role of the endothelium in modulation of the acetylcholine vasoconstrictor response in porcine coronary microvessels

Myers, Paul R.; Banitt, Peter F.; Guerra, Ricardo; Harrison, David G.

doi:10.1093/cvr/25.2.129

Cited by 30 publications

(24 citation statements)

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“…These experiments suggest that ACh may cross the endothelium to act directly on muscarinic receptors on the vascular smooth muscle. In contrast, Myers et al (22) have shown that an ACh-induced contraction in large coronary arteries of pigs is augmented by agents that inactivate or inhibit the synthesis of EORF. However, Myers et af.…”

Section: Discussionmentioning

confidence: 84%

“…However, Myers et af. (22) and Christie et af. (23) found no evidence for ACh-stimulated EORF release, although EORF was not actually measured.…”

Section: Discussionmentioning

confidence: 95%

“…Thromboxane A 2 or prostaglandin endoperoxide could be involved in the vasoconstrictor process (24), inasmuch as Wagerle and Busija (25) have shown recently that these prostanoids play an important role in cerebrovascular constrictor responses to ACh in piglets. Moreover, Myers et al (22) have shown that ACh's vasoconstriction in isolated, epicardial coronary arteries of the pig is, in part , mediated by a cyclooxygenase product, inasmuch as the vasoconstriction is attenuated by indomethacin. Our results are consistent with these findings, although our whole heart preparation does not allow us to distinguish which coronary artery segments may be more or less responsive to the effects of indomethacin.…”

Section: Discussionmentioning

confidence: 99%

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Acetylcholine-Induced Coronary Vasoconstriction and Negative Inotropy in the Neonatal Pig Heart

Ascuitto¹,

Ross-Ascuitto²,

Ramage³

et al. 1992

Pediatr Res

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ABSTRACf. We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP , bradykinin, and substance P on coronary vascular tone in isolated , neonatal pig hearts (s4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion , with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (~2.5 mL/min/g) corresponding to a perfusion pressure of~60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 JLL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilatation) by 16.9 ± 1.2, 25.3 ± 4.4, 18.3 ± 1.2, 18.9 ± 1.4, and 7.1 ± 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 ± 0.8 and 3.8 ± 0.5 mm Hg, respectivel y, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pre ssure (vasoconstriction) by 16.7 ± 2.7, 48.2 ± 8.2, and 85.3 ± 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pres sure from 108.7 ± 5.0 to 69.2 ± 4.6, 56.3 ± 6.1, and 48.2 ± 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10-6 M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87% ,66%, and 48%, respectively. In other hearts, the calcium channel antagonist, nisoldipine (10-7 M), reduced the peak change in perfusion pre ssure for the 5,20, and 100 nmol doses of acetylcholine by 87 %, 77%, and 56%, respectivel y. In summary, acetylcholine causes predominantly coronary vasoconstrictive and negative inotropic effects in neonatal pig hearts; both actions are muscarinic receptor mediated. Our data also indicate that a cyclooxygenase product may, in part, be involved in this vasoconstriction, and that an extracellular source of calcium contributes to the vasoconstrictive process. (Pediatr Res 32: 236-242, 1992) Abbreviations ACh, acet ylcholine EDRF, endothelium-derived relaxing factor BK, brad ykinin sub P, substance P NO , nitric oxide PSP, peak systolic pressure dP/dt, change in pressure per unit time Some 30 years ago, Cassin et al. (I) showed that ACh dilates the normally high tone pulmonary vasculature of the fetus. More recently, ACh has been shown to be a potent dilator of precontra cted, isolated systemic and pulmon ary arteries from neonates of several species (2). As originally demonstrated by Furchgott and Zawadzki (3), the vasorelaxation produced by ACh requires the presence of a functionally intact end othel ium and involves the produ ction of an EDRF. ACh has also been shown to relax precontracted, epicardial coro nary arteries isolated from several species, mo st notably the dog (4). It has becom e apparent, however, that the se results cannot b...

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Section: Discussionmentioning

confidence: 84%

“…However, Myers et af. (22) and Christie et af. (23) found no evidence for ACh-stimulated EORF release, although EORF was not actually measured.…”

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Acetylcholine-Induced Coronary Vasoconstriction and Negative Inotropy in the Neonatal Pig Heart

Ascuitto¹,

Ross-Ascuitto²,

Ramage³

et al. 1992

Pediatr Res

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“…Besides the ethical aspects of animal models, care must be taken when generalising the results gained in animal models to humans. For example, ACh initiates an endothelium-dependent dilation in human ventricular arterioles, while in the porcine circulation an endothelium-independent constriction is observed (Gutterman et al, 2016;Myers et al, 1991).…”

Section: Experimental Models For Studying Microvascular Functionmentioning

confidence: 99%

Assessment of microvascular and metabolic responses in the skin

Iredahl¹

2016

Linköping University Medical Dissertations

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The general aim of this project was to develop experimental in vivo models that allow for minimally invasive investigations of responses in the skin to microvascular and metabolic provocations. The cutaneous microvasculature has emerged as a valuable model and been proposed to mirror the microcirculation in other organs. Dysfunction in the cutaneous microcirculation has thus been linked to systemic diseases such as hypertension and diabetes mellitus. Models for investigating skin responses could facilitate the understanding of pathophysiological mechanisms as well as effects of drugs. In the first study, three optical measurement techniques (laser Doppler flowmetry (LDF), laser speckle contrast imaging (LSCI) and tissue viability imaging (TiVi)) were compared against each other and showed differences in their ability to detect microvascular responses to provocations in the skin. TiVi was found more sensitive for measurement of noradrenaline-induced vasoconstriction, while LSCI was more sensitive for measurement of vascular occlusion. In the second study, microvascular responses in the skin to iontophoresis of vasoactive drugs were found to depend on the drug delivery protocol. Perfusion half-life was defined and used to describe the decay in the microvascular response to a drug after iontophoresis. In the third study, the role of nitric oxide (NO) was assessed during iontophoresis of insulin. The results showed a NO-dependent vasodilation in the skin by insulin. In the fourth study the vasoactive and metabolic effects of insulin were studied after both local and endogenous administration. Local delivery of insulin increased skin blood flow, paralleled by increased skin concentrations of interstitial pyruvate and lactate, although no change in glucose concentration was observed. An oral glucose load resulted in an increased insulin concentration in the skin paralleled by an increase in blood flow, as measured using the microdialysis urea clearance technique, although no changes in perfusion was measured by LSCI. The thesis concludes that when studying skin microvascular responses, the choice of measurement technique and the drug delivery protocol has an impact on the measurement results, and should therefore be carefully considered. The thesis also concludes that insulin has metabolic and vasodilatory effects in the skin both when administered locally and as an endogenous response to an oral glucose load. The vasodilatory effect of insulin in the skin is mediated by nitric oxide

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“…On the basis of these findings, further studies evaluating therapeutic approaches for improving microvascular integrity at the acute phase of STEMI that might improve infarct healing and functional recovery are warranted. Sodium nitroprusside (NTP), which is a direct donor of nitric oxide, 5) strongly dilates the resistance arterioles and plays a significant role in coronary blood flow through the microcirculation, 6,7) and requires no intracellular metabolism to derive nitric oxide. Thus, this study was planned to evaluate the effect of intracoronary administration of NTP on impaired microcirculation in patients who underwent PCI for STEMI.…”

Section: )mentioning

confidence: 99%

Acute Effect of Sodium Nitroprusside on Microvascular Dysfunction in Patients Who Underwent Percutaneous Coronary Intervention for Acute ST-segment Elevation Myocardial Infarction

Morimoto¹,

Ito²,

Nakasuka³

et al. 2012

Int. Heart J.

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SummaryEven in the era of thrombus aspiration and distal protection for ST-segment elevation acute myocardial infarction (STEMI), microvascular dysfunction does exist and improvement of microvascular dysfunction can improve the prognosis and/or left ventricular dysfunction. We evaluated the acute effects of nitroprusside (NTP) on coronary microvascular injury that occurred after primary percutaneous coronary intervention (PCI) for STEMI in 18 patients. The final Thrombolysis in Myocardial Infarction trial (TIMI) flow grade after PCI was 3 in 17 patients and 2 in 1 patient. The index of microcirculatory resistance (IMR) was improved significantly from 76 ± 42 to 45 ± 37 (P = 0.0006) by intracoronary NTP administration. IMR improved to the normal range (IMR < 30) in 9 patients (50%). Higher TIMI flow grade and lower IMR at baseline were observed more frequently in patients whose IMR recovered to normal range after NTP administration. NTP improved the microcirculatory dysfunction at the acute phase in patients who underwent PCI for STEMI and had final TIMI 3 flow in almost all cases. (Int Heart J 2012; 53: 337-340) Key words: Acute myocardial infarction, Reperfusion, Index of microcirculatory resistance, Slow flow, Complication S everal methods have been proposed to evaluate the prognosis of patients with acute myocardial infarction (AMI) who underwent percutaneous coronary intervention (PCI). Despite the importance of microvascular coronary dysfunction for a prognosis, accurate estimation of microvascular function is challenging immediately after reperfusion for AMI. Although epicardial coronary blood flow at final angiography is one of the predictive factors with which to evaluate left ventricular function recovery in the chronic stage, thrombolysis in myocardial infarction trial (TIMI) flow grade 3 is not adequate and more accurate modalities have been reported, such as the corrected TIMI flow count 1) and Blush score. 2)Fearon, et al 3) reported that, compared to other traditional methods for assessing the microcirculation, the index of microcirculatory resistance (IMR) is a better predictor of microvascular damage and recovery of left ventricular function after STsegment elevation AMI (STEMI). Sezer, et al 4) also reported that the IMR measured early (2 days) after STEMI independently predicted the infarct size at follow-up (5 months). Treatment for microcirculation injury after PCI for an occluded coronary artery is important, although evidence showing its effect is scarce. On the basis of these findings, further studies evaluating therapeutic approaches for improving microvascular integrity at the acute phase of STEMI that might improve infarct healing and functional recovery are warranted. Sodium nitroprusside (NTP), which is a direct donor of nitric oxide, 5) strongly dilates the resistance arterioles and plays a significant role in coronary blood flow through the microcirculation, 6,7) and requires no intracellular metabolism to derive nitric oxide. Thus, this study was planned to evaluate the effect o...

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Role of the endothelium in modulation of the acetylcholine vasoconstrictor response in porcine coronary microvessels

Cited by 30 publications

References 0 publications

Acetylcholine-Induced Coronary Vasoconstriction and Negative Inotropy in the Neonatal Pig Heart

Acetylcholine-Induced Coronary Vasoconstriction and Negative Inotropy in the Neonatal Pig Heart

Assessment of microvascular and metabolic responses in the skin

Acute Effect of Sodium Nitroprusside on Microvascular Dysfunction in Patients Who Underwent Percutaneous Coronary Intervention for Acute ST-segment Elevation Myocardial Infarction

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