Microvascular oxygen delivery and consumption following treatment with verapamil

2005 ◽  
Vol 288 (4) ◽  
pp. H1515-H1520 ◽  
Author(s):  
Nanae Hangai-Hoger ◽  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
Pedro Cabrales ◽  
Marcos Intaglietta

The microvascular distribution of oxygen was studied in the arterioles and venules of the awake hamster window chamber preparation to determine the contribution of vascular smooth muscle relaxation to oxygen consumption of the microvascular wall during verapamil-induced vasodilatation. Verapamil HCl delivered in a 0.1 mg/kg bolus injection followed by a continuous infusion of 0.01 mg·kg−1·min−1 caused significant arteriolar dilatation, increased microvascular flow and functional capillary density, and decreased arteriolar vessel wall transmural Po2 difference. Verapamil caused tissue Po2 to increase from 25.5 ± 4.1 mmHg under control condition to 32.0 ± 3.7 mmHg during verapamil treatment. Total oxygen released by the microcirculation to the tissue remained the same as at baseline. Maintenance of the same level of oxygen release to the tissue, increased tissue Po2, and decreased wall oxygen concentration gradient are compatible if vasodilatation significantly lowers vessel wall oxygen consumption, which in this model appears to constitute an important oxygen-consuming compartment. These findings show that treatment with verapamil, which increases oxygen supply through vasodilatation, may further improve tissue oxygenation by lowering oxygen consumption of the microcirculation.

2004 ◽  
Vol 287 (4) ◽  
pp. H1792-H1800 ◽  
Author(s):  
B. Friesenecker ◽  
A. G. Tsai ◽  
M. W. Dünser ◽  
A. J. Mayr ◽  
J. Martini ◽  
...  

The microvascular distribution of oxygen was studied in the arterioles and venules of the awake hamster window chamber preparation to determine the contribution of vascular smooth muscle contraction to oxygen consumption of the microvascular wall during arginine vasopressin (AVP)-induced vasoconstriction. AVP was infused intravenously at the clinical dosage (0.0001 IU·kg−1·min−1) and caused a significant arteriolar constriction, decreased microvascular flow and functional capillary density, and a substantial rise in arteriolar vessel wall transmural Po2 difference. AVP caused tissue Po2 to be significantly lowered from 25.4 ± 7.4 to 7.2 ± 5.8 mmHg; however, total oxygen extraction by the microcirculation increased by 25%. The increased extraction, lowered tissue Po2, and increased wall oxygen concentration gradient are compatible with the hypothesis that vasoconstriction significantly increases vessel wall oxygen consumption, which in this model appears to constitute an important oxygen-consuming compartment. This conclusion was supported by the finding that the small percentage of the vessels that dilated in these experiments had a vessel wall oxygen gradient that was smaller than control and which was not determined by changes in tissue Po2. These findings show that AVP administration, which reduces oxygen supply by vasoconstriction, may further impair tissue oxygenation by the additional oxygen consumption of the microcirculation.


1991 ◽  
Vol 260 (3) ◽  
pp. H698-H701 ◽  
Author(s):  
J. L. Dinerman ◽  
D. L. Lawson ◽  
J. L. Mehta

To evaluate the role of endothelium in nitroglycerin (NTG)-mediated vascular relaxation, epinephrine-contracted rat thoracic aortic segments with and without intact endothelium were exposed to NTG (10(-10) to 10(-5) M). Aortic segments with intact (endo+, n = 15) and denuded endothelium (endo-, n = 9) exhibited typical NTG-induced relaxation. However, the mean effective concentration of NTG was lower for endo- than for endo+ segments (P less than 0.001). To determine if this phenomenon related to nitric oxide (NO) generation by endothelium, six endo+ segments were treated with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of NO production. These endo+ segments exhibited greater (P less than 0.001) relaxation in response to NTG than the untreated endo+ segments. Oxyhemoglobin, an inhibitor of guanylate cyclase activation, greatly diminished NTG-mediated relaxation of all aortic segments. To determine if the enhanced NTG-mediated relaxation of endo- segments was unique to the guanosine 3',5'-cyclic monophosphate-dependent vasodilator NTG, other endo+ and endo- segments were exposed to adenosine 3',5'-cyclic monophosphate-dependent vasodilator papaverine (10(-8) to 10(-4) M), and no difference in EC50 was noted between endo+ and endo- segments. Thus endothelium attenuates NTG-mediated vasorelaxation, and this attenuation is abolished by inhibition of endothelial NO production with L-NMMA. These observations indicate that endothelium is a dynamic modulator of vascular smooth muscle relaxant effects of NTG. This modulation appears to result from a competitive interaction between endothelial NO and NTG.


1996 ◽  
Vol 61 (2) ◽  
pp. 444-448 ◽  
Author(s):  
David A. Fullerton ◽  
Jeanette Agrafojo ◽  
Robert C. McIntyre, Jr.

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