Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine

Mügge, Andreas; López, J. Antonio G.; Piegors, Donald J.; Breese, Keith; Heistad, Donald D.

doi:10.1152/ajpheart.1991.260.1.h242

Cited by 63 publications

(55 citation statements)

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“…As L-arginine did not prevent or reverse the effects of L-NAME in those studies (Broten et al, 1992;McMahon et al, 1992) (Shirasaki & Su, 1985;Mugge et al, 1991). Since baseline perfusion pressure was not significantly altered after treatment with L-NOARG or CHAPS, the enhanced dilator response to SNP is likely to be due to the reported increased sensitivity of guanylate cyclase to exogenous NO when basal NO release is impaired (Moncada et al, 1991b).…”

Section: Baseline Perfusion Pressurementioning

confidence: 86%

Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

Loke

Sobey

Dusting

et al. 1994

British J Pharmacology

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1 We aimed to determine whether nitric oxide (NO) and/or the endothelium is involved in cholinergic neurogenic vasodilatation in the rat isolated hindquarters. 2 The abdominal aorta was cannulated for perfusion of the rat hindquarters with Krebs bicarbonate solution containing phenylephrine, to induce basal constrictor tone. In the presence of noradrenergic neurone blockade with guanethidine (200 mg kg', i.p.) electrical stimulation of peri-aortic nerves induced frequency-dependent decreases in hindquarters perfusion pressure, indicating vasodilatation. Both the endothelium-dependent vasodilator, acetylcholine (ACh) and the endothelium-independent vasodilator, sodium nitroprusside (SNP) induced dose-dependent decreases in perfusion pressure. In each experiment, responses to either nerve stimulation, ACh or SNP were recorded before and after treatment with saline vehicle, atropine (1 gLM), NG-nitro-L-arginine (L-NOARG, 100 JM), L-arginine (1 mM), L-arginine plus L-NOARG, or 3-3 cholamidopropyl dimethylammonio 1-propanesulphonate (CHAPS, 30 mg). Hindquarters dilatation after each treatment was expressed as a percentage of the control response. 3 Following treatment with saline, responses to nerve stimulation and ACh were 99 ± 9% and 107 ± 10% of control, respectively demonstrating the reproducibility of these responses. Nerve stimulation-induced dilatation was abolished by atropine (0 ± 0% of control, P <0.05) or reduced to 14 ± 10% of control by NO synthase inhibition with L-NOARG (P <0.05). Dilator responses to ACh were also abolished by atropine (0 ± 0% of control, P<0.05) or inhibited by L-NOARG (59 ± 10% of control, P<0.05), indicating that the neurogenic dilatation is cholinergic and is mediated by NO. The administration of the NO precursor, L-arginine, prevented the inhibitory effect of L-NOARG on dilator responses to nerve stimulation and ACh (L-arginine plus L-NOARG: 89 ± 13% and 122 ± 24% of control, respectively). In addition CHAPS, which removes endothelial cells, inhibited responses to both nerve stimulation (0 ± 0% of control, P <0.05) and ACh (33 ± 8% of control, P <0.05). In contrast, no treatment significantly reduced the vasodilator responses to SNP. 4 These observations suggest that cholinergic neurogenic vasodilatation in the rat isolated hindquarters requires the synthesis and release of NO from the endothelium.

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Section: Baseline Perfusion Pressurementioning

confidence: 86%

Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

Loke

Sobey

Dusting

et al. 1994

British J Pharmacology

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“…The mesentery of a group of 12 rabbits (L-NA group; see Table 1) was superfused with L-NA in a concentration of 0.1 mmol/L; this concentration has been shown to be high enough to effectively inhibit NOS in rabbit tissues and blood cells. [21][22][23][24][25] Moreover, superfusion of higher L-NA concentrations results in an undesirable rise of systemic blood pressure (M.A.W.B., unpublished observations, 1995). In the control group (CON; 14 rabbits; see Table 1), the mesentery was superfused with the vehicle, a buffered Tyrode's solution.…”

Section: Superfusion Of the Mesentery With L-na Vehicle Or Combinatmentioning

confidence: 99%

“…19 In the mesentery of anesthetized rabbits, the wall of arterioles and venules was punctured with a micropipet, and the ensuing thromboembolic reaction was studied with the use of intravital videomicroscopy. In the first series of experiments, the mesentery of one group of rabbits was locally superfused with L-NA or its vehicle; L-NA is an irreversible inhibitor of NOS 5 in the wall of rabbit blood vessels [21][22][23] and in rabbit platelets. 24,25 To provide evidence that NO production was indeed inhibited under L-NA superfusion, a second series of control experiments was performed.…”

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confidence: 99%

Endogenous Nitric Oxide Protects Against Thromboembolism in Venules But Not in Arterioles

Broeders

Tangelder

Slaaf

et al. 1998

ATVB

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Abstract-Because nitric oxide (NO) inhibits aggregation and adhesion of blood platelets, NO may play a role in platelet-vessel wall interactions. Therefore, the purpose of this study was to investigate the involvement of endogenous NO in thromboembolic processes, as induced by wall puncture, in rabbit mesenteric arterioles and venules (diameters 20 to 43 m). In venules, inhibition of NO synthase by superfusion of the mesentery with N -nitro-L-arginine (L-NA; 0.1 mmol/L) significantly increased the duration of embolization (from 50 seconds to 511 seconds) and the number of emboli produced (from 2 to 11 emboli per vessel), while the median period of time needed to produce an embolus was not influenced. On the contrary, in arterioles, L-NA had no significant effect on embolization (duration of embolization: 426 seconds in the control and 382 seconds in the L-NA group, with 20 and 12 emboli per vessel, respectively). Addition to the L-NA superfusate of L-arginine (L-ARG; 1 mmol/L), the active precursor for endogenous NO synthesis, resulted in a complete reversal of the L-NA effects in venules, while addition of the inactive D-arginine (D-ARG; 1 mmol/L) had no effect. Addition of L-ARG and D-ARG had no significant effect in arterioles. Addition to the L-NA superfusate of the exogenous NO donor sodium nitroprusside (0.1 mol/L) also resulted in reversal of the L-NA effects in venules, while in arterioles, it slightly but significantly decreased embolization duration. The differences in effect of L-NA on embolization between arterioles and venules were not caused by differences in fluid dynamic conditions. It is concluded that the role of endogenous NO in inhibiting thromboembolic processes is more important in venules than in arterioles.

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“…Thus, in isolated blood vessels and intact circulation, the action of endothelial vasodilators is, at least in part, resistant to NO inhibitors. 4,5 An alternative mechanism is an endothelial factor that causes hyperpolarization of smooth muscle cells, 6 possibly mediated by an increase in conductivity to potassium ions, 7,8 activation of Na ϩ K ϩ /ATPase, or inactivation of chloride channels. 9 In healthy human subjects, several agonists (including acetylcholine and bradykinin) cause vasodilation when directly injected into the brachial or coronary circulation.…”

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confidence: 99%

Vasodilation to Bradykinin Is Mediated by an Ouabain-Sensitive Pathway as a Compensatory Mechanism for Impaired Nitric Oxide Availability in Essential Hypertensive Patients

et al. 1999

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Background —In essential hypertension, endothelium-dependent vasodilation is impaired because of reduced nitric oxide (NO) availability, which is mainly caused by oxidative stress. The present study was designed to identify the mechanism(s) responsible for NO-independent vasodilation to bradykinin in patients with essential hypertension. Methods and Results —In 16 healthy subjects (49.5±5.8 years; 118.6±3.5/78.9±2.9 mm Hg) and 16 patients with essential hypertension (47.9±4.8 years; 154.6±4.5/102.9±3.2 mm Hg), we measured modifications in forearm blood flow (strain-gauge plethysmography) during intrabrachial infusion of bradykinin (5, 15, or 50 ng/100 mL of forearm tissue per minute) in the presence of saline, N ω -monomethyl- l -arginine (L-NMMA; used to inhibit NO synthase; 100 μg/100 mL of forearm tissue per minute), and ouabain (to block Na + K + /ATPase and prevent hyperpolarization; 0.7 μg/100 mL of forearm tissue per minute). In healthy subjects, vasodilatation to bradykinin was significantly blunted by L-NMMA and unaffected by ouabain. In hypertensive patients, vasodilatation to bradykinin was not modified by L-NMMA, but it was significantly reduced by ouabain. In an adjunctive group of 8 hypertensive patients (49.9±3.8 years; 155.9±5.5/103.7±3.9 mm Hg), the response to bradykinin was repeated during the administration of intrabrachial vitamin C (a scavenger for oxygen free radicals; 8 mg/100 mL of forearm tissue per minute). In these patients, L-NMMA–induced inhibition of vasodilation to bradykinin was restored, and ouabain was no longer effective. In a final group of 6 normotensive controls (45.9±4.1 years; 115.1±2.9/79.3±2.1 mm Hg), vasodilation to bradykinin residual to L-NMMA blockade was further inhibited by simultaneous ouabain infusion. Conclusions —Vasodilation to bradykinin is impaired in essential hypertensive patients because of an NO-system alteration caused by oxidative stress, and it is mediated by an alternative pathway, possibly involving endothelium-dependent hyperpolarization.

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Acetylcholine-induced vasodilatation in rabbit hindlimb in vivo is not inhibited by analogues of L-arginine

Cited by 63 publications

References 0 publications

Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

Requirement for endothelium‐derived nitric oxide in vasodilatation produced by stimulation of cholinergic nerves in rat hindquarters

Endogenous Nitric Oxide Protects Against Thromboembolism in Venules But Not in Arterioles

Vasodilation to Bradykinin Is Mediated by an Ouabain-Sensitive Pathway as a Compensatory Mechanism for Impaired Nitric Oxide Availability in Essential Hypertensive Patients

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