Arteriolar tone is determined by activity of ATP-sensitive potassium channels

The role of ATP-sensitive potassium channels (KATP) in determining resting arteriolar tone and vasodilator reactivity was assessed in superfused, hamster microcirculatory beds studied via intravital microscopy. Under resting conditions, the selective KATP blocker, glibenclamide, produced concentration-dependent vasoconstriction in both the cheek pouch and the cremaster muscle. Concentration-related constriction of cheek pouch arterioles was also observed with tetrapentylammonium, although this agent appeared to have toxic effects on the microcirculation. Glibenclamide (2 microM) abolished arteriolar vasodilation to cromakalim and pinacidil over a concentration range (10 nM-1 microM) in which these agents are selective KATP agonists and also significantly inhibited adenosine-, carbacyclin-, and isoproterenol-induced vasodilation. In contrast, responses to other vasodilators were not significantly affected [methacholine, forskolin, and dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP)] or only slightly depressed (sodium nitroprusside). Thus the activity of KATP determines, in part, resting arteriolar tone in the hamster. Furthermore, vasodilators like adenosine, beta-adrenergic agonists, and prostacyclin appear to act through these ion channels by a mechanism that may not involve cAMP.

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Prostaglandins do not mediate arteriolar oxygen reactivity

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1986.250.6.h1102 ◽

1986 ◽

Vol 250 (6) ◽

pp. H1102-H1108 ◽

Cited By ~ 4

Author(s):

W. F. Jackson

Keyword(s):

Arachidonic Acid ◽

Phospholipase A2 ◽

Intravital Microscopy ◽

Cheek Pouch ◽

Cyclooxygenase Inhibitor ◽

Cremaster Muscle ◽

Hamster Cheek Pouch ◽

Nonspecific Effects ◽

Oxygen Reactivity ◽

Phospholipase A2 Inhibitors

The hypothesis that prostaglandins mediate arteriolar O2 reactivity was tested by assessing the effects of cyclooxygenase and phospholipase A2 inhibitors on the O2 responses of arterioles in superfused hamster cheek pouch and hamster and rat cremaster muscle preparations by use of intravital microscopy. Superfusion of these three preparations with the cyclooxygenase inhibitor indomethacin (50 microM) completely inhibited the response of the vessels to exogenous arachidonic acid but had no effect on the arteriolar constriction induced by elevation of superfusion solution PO2 from 15 to 150 mmHg. Similar results were obtained in the hamster cheek pouch with another cyclooxygenase inhibitor, meclofenamate, or when indomethacin (5-50 mg/kg) was administered systemically. Dexamethasone (12.7 microM) and quinacrine (10 microM), two reported inhibitors of phospholipase A2, also had no significant effect on arteriolar O2 reactivity in the cheek pouch. At 50 microM, quinacrine significantly depressed arteriolar reactivity to O2, adenosine, methacholine, and phenylephrine, suggesting nonspecific effects. These data do not support the hypothesis that prostaglandins mediate arteriolar O2 reactivity.

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Role of Potassium Channels in Regulation of Brain Arteriolar Tone

Stroke ◽

10.1161/01.str.32.1.218 ◽

2001 ◽

Vol 32 (1) ◽

pp. 218-224 ◽

Cited By ~ 34

Author(s):

Tetsuyoshi Horiuchi ◽

Hans H. Dietrich ◽

Shinichiro Tsugane ◽

Ralph G. Dacey

Keyword(s):

Potassium Channels ◽

Arteriolar Tone

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Cytochrome P-450 ω-hydroxylase senses O2 in hamster muscle, but not cheek pouch epithelium, microcirculation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1999.276.2.h503 ◽

1999 ◽

Vol 276 (2) ◽

pp. H503-H508 ◽

Cited By ~ 17

Author(s):

Julian H. Lombard ◽

Mary Pat Kunert ◽

Richard J. Roman ◽

John R. Falck ◽

David R. Harder ◽

...

Keyword(s):

Regional Differences ◽

Selective Inhibitor ◽

Cheek Pouch ◽

Retractor Muscle ◽

Cremaster Muscle ◽

Suicide Substrate ◽

Male Golden Hamsters ◽

Substrate Inhibitor ◽

Cytochrome P 450

The goal of this study was to investigate the role of cytochrome P-450 ω-hydroxylase in mediating O2-induced constriction of arterioles in the microcirculation of the hamster. Male Golden hamsters were anesthetized with pentobarbital sodium, and the cremaster muscle or cheek pouch was prepared for observation by intravital microscopy. Arteriolar diameters were measured during elevations of superfusate[Formula: see text] from ∼5 to 150 mmHg. Arteriolar responses to elevated [Formula: see text] were determined in the cremaster muscle, in the retractor muscle where it inserts on the cheek pouch, and in the epithelial portion of the cheek pouch. Elevation of superfusion solution[Formula: see text] caused a vigorous constriction of arterioles in the cremaster and retractor muscles and in the epithelial portion of the cheek pouch. Superfusion with 10 μM 17-octadecynoic acid, a suicide substrate inhibitor of cytochrome P-450 ω-hydroxylase, and intravenous infusion of N-methylsulfonyl-12,12-dibromododec-11-enamide, a mechanistically different and highly selective inhibitor of cytochrome P-450 ω-hydroxylase, caused a significant reduction in the magnitude of O2-induced constriction of arterioles in the cremaster and retractor muscles. However, arteriolar constriction in response to elevated[Formula: see text] was unaffected by 17-octadecynoic acid or N-methylsulfonyl-12,12-dibromododec-11-enamide in the epithelial portion of the cheek pouch. These data confirm that there are regional differences in the mechanism of action of O2 on the microcirculation and indicate that cytochrome P-450 ω-hydroxylase senses O2 in the microcirculation of hamster skeletal muscle, but not in the cheek pouch epithelium.

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Effect of cigarette smoke extract on arteriolar dilatation in vivo

Journal of Applied Physiology ◽

10.1152/jappl.1996.81.5.1996 ◽

1996 ◽

Vol 81 (5) ◽

pp. 1996-2003 ◽

Cited By ~ 26

Author(s):

William G. Mayhan ◽

Glenda M. Sharpe

Keyword(s):

Potassium Channels ◽

Adenylate Cyclase ◽

Cigarette Smoke ◽

Intravital Microscopy ◽

Cigarette Smoke Extract ◽

Cheek Pouch ◽

Hamster Cheek Pouch ◽

Baseline Diameter

Mayhan, William G., and Glenda M. Sharpe. Effect of cigarette smoke extract on arteriolar dilatation in vivo. J. Appl. Physiol. 81(5): 1996–2003, 1996.—The goal of this study was to determine whether cigarette smoke extract alters dilatation of arterioles in vivo in response to agonists that produce activation of ATP-sensitive potassium channels and activation of adenylate cyclase. By using intravital microscopy, we measured diameter of arterioles contained within the microcirculation of the hamster cheek pouch during suffusion with agonists in the absence and presence of cigarette smoke extract (0.1, 0.5, and 1.0%). Before treatment with cigarette smoke extract, activation of ATP-sensitive potassium channels with aprikalim and cromakalim produced dose-related dilatation of cheek pouch arterioles. Similarly, activation of adenylate cyclase with isoproterenol and forskolin produced dose-related dilatation of cheek pouch arterioles before treatment with cigarette smoke extract. Superfusion of 0.1% cigarette smoke extract did not change baseline diameter of arterioles and did not alter responses of cheek pouch arterioles to activation of ATP-sensitive potassium channels and adenylate cyclase. Superfusion of 0.5 and 1.0% cigarette smoke extract also did not alter baseline diameter of arterioles but did impair dilatation of arterioles in response to activation of ATP-sensitive potassium channels and adenylate cyclase. These findings suggest that cigarette smoke extract impairs dilatation of resistance arterioles in response to activation of important cellular dilator pathways.

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Role of venular endothelium in control of arteriolar diameter during functional hyperemia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1994.267.3.h1227 ◽

1994 ◽

Vol 267 (3) ◽

pp. H1227-H1231 ◽

Cited By ~ 17

Author(s):

Y. Saito ◽

A. Eraslan ◽

V. Lockard ◽

R. L. Hester

Keyword(s):

Silver Chloride ◽

Muscle Stimulation ◽

Functional Hyperemia ◽

Cremaster Muscle ◽

Silver Silver ◽

Silver Silver Chloride ◽

Arteriolar Vasodilation ◽

Venular Endothelium

This study was designed to determine the importance of the venular endothelium in the vasodilation of adjacent arterioles during functional hyperemia. The hamster cremaster muscle was prepared for in vivo microscopy. Two silver-silver chloride electrodes were placed across the pedicle of the cremaster muscle, and a square-wave pulse (10 V amplitude, 1 ms duration, and 1 Hz frequency) was used to elicit muscle contraction. Muscle stimulation for 1 min resulted in a vasodilation of the first-order arterioles from 74 +/- 2 to 91 +/- 2 microns (n = 9, P < 0.05). After perfusion of the venule with air to disrupt the venular endothelium, there was no significant effect on the resting diameter, 73 +/- 3 microns, but the vasodilation associated with the muscle stimulation was significantly attenuated to 82 +/- 3 microns (P < 0.01). After completion of these experiments, the disruption of venular endothelium was confirmed by electron microscopy. The functional vasodilation of arterioles adjacent to venules with an intact endothelium (venules in which air did not enter) was retained after air perfusion (n = 6). These results suggest that the presence of the venular endothelium is important for the arteriolar vasodilation during functional hyperemia. We propose that the venular endothelium releases a relaxing factor responsible for a portion of the functional arteriolar vasodilation.

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