Analysis of responses to bradykinin in the pulmonary vascular bed of the cat

DeWitt, Bracken J.; Cheng, David Y.; McMahon, Timothy J.; Nossaman, Bobby D.; Kadowitz, Philip J.

doi:10.1152/ajpheart.1994.266.6.h2256

Cited by 17 publications

(14 citation statements)

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“…These results show the hindlimb vasodilator responses to PN, and to the NO donors, sodium nitroprusside and DEA/NO, were enhanced in duration at a time when vasodilator responses to the beta 2 receptor agonist, albuterol, were not altered. These data along with the observation that the type 4 cAMP phosphodiesterase inhibitor, rolipram, did not alter the duration of the response to PN, provides evidence in support of the hypothesis that PN induced vasodilation in the cat circulation is mediated, at least, in part by a cGMP-dependent mechanism [222,223]. Although experiments with zaprinast provide evidence in support of a cGMP dependent mechanism, additional support for this mechanism could be derived from experiments with inhibitors of guanylate cyclase and of cGMP dependent protein kinase.…”

Section: Vasorelaxant Properties Of Peroxyni-tritesupporting

confidence: 62%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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Peroxynitrite (PN) is generated by the reaction of nitric oxide (NO) and superoxide in one of the most rapid reactions in biology. Studies have reported that PN is a cytotoxic molecule that contributes to vascular injury in a number of disease states. However, it has become apparent that PN has beneficial effects including vasodilation, inhibition of platelet aggregation, inhibition of inflammatory cell adhesion, and protection against ischemia/reperfusion injury in the heart. It is our hypothesis that PN may serve to inactivate superoxide and prolong the actions of NO in the circulation. This manuscript reviews the beneficial effects of PN in the cardiovascular system. Keywords:Nitric oxide/*metabolism, nitric oxide synthase/metabolism/physiology, peroxynitrous acid/metabolism, reactive nitrogen species/metabolism, reactive oxygen species/metabolism, endothelium, vascular/drug effects/metabolism, muscle, smooth, vascular/drug effects/*metabolism, vasodilator agents/adverse effects, oxidative stress/*physiology, vasodilation/drug effects.

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Section: Vasorelaxant Properties Of Peroxyni-tritesupporting

confidence: 62%

Potential Benefits of Peroxynitrite

Nossaman

Kadowitz²

2008

TOPHARMJ

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“…The results of the present studies suggest, however, that kinin B1 and B2 receptors mediating the release of nitric oxide are present on endothelial cells in the pulmonary vascular bed of the cat. 34,35,37 Although the present data suggest that DABK increases lobar arterial pressure by releasing catecholamines in the lung and activating a-adrenergic receptors under low-tone conditions but decreases lobar arterial pressure by releasing nitric oxide under elevated-tone conditions, the exact mechanism by which the increase in tone changes the direction and mechanism of the response is uncertain. Since both pressor and depressor responses are reduced by des-Arg9,[Leu8]-BK, they are mediated by activation of kinin Bi receptors.…”

Section: Responses To Dabk Under Elevated-tone Conditionsmentioning

confidence: 72%

des-Arg9-bradykinin produces tone-dependent kinin B1 receptor-mediated responses in the pulmonary vascular bed.

DeWitt

Cheng

Kadowitz

1994

Circulation Research

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Responses to des-Arg'-bradykinin, a selective kinin Bi receptor agonist, were characterized in the pulmonary vascular bed of the intact-chest cat. Injections of des-Arg'-bradykinin into the perfused lobar artery under low-resting tone conditions caused dose-related increases in lobar arterial pressure; whereas in the same experiment under elevated tone responses under elevated-tone conditions were inhibited by N'-nitro-L-arginine methyl ester, suggesting that des-Arg'-bradykinin stimulates the release of nitric oxide, whereas meclofenamate and U-37883A, a nonsulfonylurea ATP-sensitive K' channel antagonist, did not alter vasodilator responses to the Bi receptor agonist. These results suggest that vasoconstrictor responses to des-Arg'-bradykinin under low-tone conditions are mediated by the activation of kinin Bi receptors, the release of catecholamines within the lung, and the activation of a-adrenergic receptors, whereas vasodilator responses under elevated tone conditions are mediated by activation of Bi receptors and the release of nitric oxide from the endothelium. These data provide pharmacologic evidence for the existence of functionally active kinin Bi receptors that mediate tone-dependent vasoconstrictor and vasodilator responses in the pulmonary vascular bed of the cat. (Circ Res. 1994;75:1064-1072 Key Words * des-Arg9-bradykinin * Hoe 140 * pulmonary vascular bed * kinin Bi receptor * nitric oxideThere is considerable pharmacologic evidence in support of the concept of BK receptor heterogeneity.2'3'13'14The classic BK receptor subtypes have been characterized as B1 and B2, and the action of BK on the B2 receptor is thought to mediate the majority of physiological responses to the kinins.23 The Bi receptor is selectively stimulated by DABK on the basis of highaffinity contractile activity of the peptide in the rabbit aorta, mesenteric vein, and basilar artery; however, this receptor is not believed to play an important role under physiological conditions.314 The development of competitive, potent, selective kinin receptor antagonists has provided support for the identity of Bi receptors.2'3 DABK does not activate B2 receptors but stimulates kinin B1 receptors, and a change in the balance between levels of BK and its metabolite, DABK, could change the emphasis and effects of the kinin system.23"15Although Bi receptors are not thought to be physiologically important in mediating cardiovascular responses to kinins, such as increased vascular permeability, smooth muscle contraction, vasodilation, and hypotension, they have recently been shown to play a role in mediating decreases in systemic arterial pressure in the dog under physiological conditions.'6-19 Kinin

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“…Zaprinast inhibits the degradation of cGMP in the vascular smooth muscle by inhibiting cGMP phosphodiesterase activity and thus increases the cellular level of cGMP, which has been shown to augment vasorelaxation to guanylyl cyclase activation in other blood vessels. 36,37 In the pilot studies, a high concentration of zaprinast (10 M) produced 10% to 15% vasodilation (n ϭ 4). To avoid the confounding effect of reducing vascular tone on lactate-induced vasodilation, we chose a lower concentration of zaprinast (1 M) for the present study.…”

Section: Discussionmentioning

confidence: 97%

Dilation of Retinal Arterioles in Response to Lactate: Role of Nitric Oxide, Guanylyl Cyclase, and ATP-Sensitive Potassium Channels

Hein

2006

Invest. Ophthalmol. Vis. Sci.

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These data suggest that uptake of lactate by vascular cells via monocarboxylate transporters causes retinal arteriolar dilation predominantly via stimulation of NO synthase and subsequent activation of guanylyl cyclase. The guanylyl cyclase/cGMP signaling triggers opening of KATP channels for vasodilation. A better understanding of the fundamental signaling pathways responsible for lactate-induced dilation of retinal arterioles may help shed light on the possible mechanisms contributing to the metabolic regulation of retinal blood flow under physiological and pathophysiological conditions.

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Analysis of responses to bradykinin in the pulmonary vascular bed of the cat

Cited by 17 publications

References 0 publications

Potential Benefits of Peroxynitrite

Potential Benefits of Peroxynitrite

des-Arg9-bradykinin produces tone-dependent kinin B1 receptor-mediated responses in the pulmonary vascular bed.

Dilation of Retinal Arterioles in Response to Lactate: Role of Nitric Oxide, Guanylyl Cyclase, and ATP-Sensitive Potassium Channels

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