Coronary Nitric Oxide Production in Response to Exercise and Endothelium-Dependent Agonists

Abstract

Background —Endothelium-derived nitric oxide (NO) contributes to epicardial coronary artery vasodilation during exercise. However, blockade of NO production does not impair the increase in coronary blood flow (CBF) during exercise, suggesting that NO is not obligatory for exercise-induced coronary resistance vessel dilation. In contrast, the increases in CBF produced by endothelium-dependent agonists are decreased after NO blockade. Consequently, this study was performed to determine whether the increase in coronary NO production in response to agonists is greater than that which occurs during exercise. Methods and Results —We measured the oxidation products of NO (nitrate+nitrite=NO x ) in aortic and coronary sinus plasma using chemiluminescence to assess NO x production across the coronary circulation in chronically instrumented dogs during a 3-stage treadmill exercise protocol and in response to intracoronary administration of the endothelium-dependent agonists acetylcholine (37.5 μg/min) and bradykinin (3.0 μg/min). No coronary NO x production could be detected at rest or during the first 2 stages of exercise; only at the highest level of exercise was a small increase in coronary NO x production measured. In contrast, coronary production of NO x was significantly increased in response to endothelium-dependent agonists. Conclusions —Coronary NO production in response to endothelium-dependent agonists is greater than in response to the increase in shear stress associated with exercise. These findings support previous studies suggesting that NO is not required for the coronary vasodilation that occurs in the normal heart during exercise.

Evaluation of bioavailability of nitric oxide in coronary circulation by direct measurement of plasma nitric oxide concentration

“…These findings coincide with ours, indicating that NO plays a pivotal role in the ACh-induced coronary vasodilation. Interestingly, they also noticed that a substantial number of animals they examined had negative arteriovenous NOx gradients between aorta and coronary sinus at rest (56). Recently, in vivo conversion of nitrite, which is the major pool of bioavailable NO, to NO has been proposed by enzymatic reduction with xanthine oxidoreductase, nonenzymatic disproportionation, or acidic reduction (57).…”

Propolis and swimming in the prevention of atherogenesis and left ventricular hypertrophy in hypercholesterolemic mice

“…Studies have shown that regular physical activity promotes the reduction of the inactivation of nitric oxide (Fogarty et al, 2004;Traverse et al, 2000), increases the production of nitric oxide (Takamura et al, 2002), increases the expression of endothelial nitric oxide synthase (eNOS) (Griffin et al, 2001) and promotes angiogenesis induced by vascular endothelial growth factor, and, with the net effect of increasing the bioavailability of nitric oxide.…”

“…Propolis is a bee product (Apis mellifera L.) which presents in its composition mainly flavonoids and other compounds (Bankova et al, 2000;Marcucci et al, 2001), and has been used in folk medicine in many countries since ancient times, because it has antioxidant, antimicrobial and anti-inflammatory properties (Wang, 1993;Marcucci, 1995;Banskota et al, 2002). In this manner, the present study aimed to verify the effect of propolis alone and its association with swimming in dyslipidemia, left ventricular hypertrophy and atherogenesis of hypercholesterolemic mice that were receiving high-fat diet.…”

“…The interaction between CD40 and CD40L activates Nfkappaβ pathway (Gelbmann et al, 2003) and promotes the phosphorylation of IKK (Kappaβ kinase inhibitor), resulting in translocation of nuclear factor kappa β (NFkappa β) to the nucleus where it activates genes involved in inflammation and cell growth (Vellaichamy et al, 2005). The NFkappa β activation participates in the development of cardiac hypertrophy in mice, characterized by increased collagen deposition (Vellaichamy et al, 2005).…”

“…The interaction between CD40 and CD40L activates Nfkappaβ pathway (Gelbmann et al, 2003) and promotes the phosphorylation of IKK (Kappaβ kinase inhibitor), resulting in translocation of nuclear factor kappa β (NFkappa β) to the nucleus where it activates genes involved in inflammation and cell growth (Vellaichamy et al, 2005). The NFkappa β activation participates in the development of cardiac hypertrophy in mice, characterized by increased collagen deposition (Vellaichamy et al, 2005). Studies have also shown that the prevention of left ventricular hypertrophy and resistance to neointimal lesion development in LDLr-/-mice fed with standard diets can be related to lower activity of the CD40/CD40L pathway due to increased plasma levels of HDL (Garcia et al, 2011).…”