2002
DOI: 10.1152/ajpheart.00429.2001
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Diminished arteriolar responses in nitrate tolerance involve ROS and angiotensin II

Abstract: Our purpose was to evaluate hyporesponsivity to nitric oxide (NO)-induced dilation in small arterioles during nitrate tolerance. An Alza osmotic pump was implanted in the left flank of adult rats (n ϭ 56) for continuous administration of nitroglycerin (140 g/h) or vehicle (propylene glycol). On postoperative day 3, arcade (ϳ50-m diameter) and terminal (ϳ20 m) arterioles were observed in the cremaster preparation with in vivo video microscopy. Local vascular responses were obtained with micropipette-applied NO … Show more

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Cited by 23 publications
(20 citation statements)
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“…101 In line with the role of ACE inhibitors, nitrate tolerance and nitrate-induced oxidative stress in animal models are markedly attenuated at the level of both conductance and resistance vessels during concomitant administration of angiotensin-1 receptor blockers. 102 Although it is unclear whether this also applies to humans, 103 given the systematic use of ACE inhibitors (eg, in the setting of congestive heart failure), these studies reinforce the concept that nitrate therapy in the modern clinical setting might have totally different implications than what is observed in experimental models (and in former clinical practice).…”
Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin-1 Rmentioning
confidence: 88%
“…101 In line with the role of ACE inhibitors, nitrate tolerance and nitrate-induced oxidative stress in animal models are markedly attenuated at the level of both conductance and resistance vessels during concomitant administration of angiotensin-1 receptor blockers. 102 Although it is unclear whether this also applies to humans, 103 given the systematic use of ACE inhibitors (eg, in the setting of congestive heart failure), these studies reinforce the concept that nitrate therapy in the modern clinical setting might have totally different implications than what is observed in experimental models (and in former clinical practice).…”
Section: Angiotensin-converting Enzyme Inhibitors and Angiotensin-1 Rmentioning
confidence: 88%
“…These phenomena were prevented by concomitant treatment of angiotensin II antagonist Losartan [21]. More recently, Frame et al provided evidence that angiotensin II is involved in reduction of arteriolar responses in nitrate tolerance [24]. This is the pathophysiologic background to clinical research on the efficacy of AT 1 antagonist Losartan as a drug able to prevent the development of nitrate tolerance.…”
Section: Losartan and Prevention Of Nitrate Tolerance: Experimental Smentioning
confidence: 99%
“…The mechanism of O 2 -ؒ -induced hypertension remains unclear. O 2 -ؒ may increase BP by quenching nitric oxide (NO) [10,11] , endothelium-dependent relaxing factor (EDRF) and/or by increasing the levels of (vasoconstrictor) F 2 -isoprostanes, via nonenzymatic oxidation of arachidonic acid [12] . Endothelial dysfunction caused by long-term AngII treatment is also related to O 2 -ؒ production within the endothelium [13] .…”
Section: Introductionmentioning
confidence: 99%