Muscle microvascular oxygenation in chronic heart failure: role of nitric oxide availability

Abstract

Aim: To test the hypothesis that diminished vascular nitric oxide availability might explain the inability of individuals with chronic heart failure (CHF) to maintain the microvascular PO 2 's (PO 2mv µ O 2 delivery-to-uptake ratio) seen in healthy animals. Methods: We superfused sodium nitroprusside (SNP; 300 lm), KrebsHenseleit (control, CON) and l-nitro arginine methyl ester (l-NAME; 1.5 mm) onto the spinotrapezius muscle and measured PO 2mv by phosphorescence quenching in female Sprague-Dawley rats (n ¼ 26) at rest and during twitch contractions (1 Hz). Seven rats served as controls (Sham) while CHF was induced by myocardial infarction. CHF rats were grouped as moderate (MOD; n ¼ 15) and severe CHF (SEV; n ¼ 4) according to morphological data and baseline PO 2mv . Results: In contrast to Sham and MOD, l-NAME did not affect the PO 2mv response (dynamics and steady-state) of SEV when compared with CON. SNP restored the PO 2mv profile of SEV to that seen in Sham animals during CON. Specifically, the effect of l-NAME expressed as D(l-NAME -CON) were: Baseline PO 2mv [in mmHg, DSham ¼ )7.0 AE 1.6 (P < 0.05); DSEV ¼ )1.2 AE 2.1], end-contractions PO 2mv [in mmHg, DSham ¼ )5.0 AE 1.0 (P < 0.05); DSEV ¼ )2.5 AE 0.5] and time constant of PO 2mv decrease [in s, DSham ¼ )6.5 AE 3.0 (P < 0.05); DSEV ¼ )3.2 AE 1.8]. Conclusion: These data provide the first direct evidence that the pathological profiles of PO 2mv associated with severe CHF can be explained, in part, by a diminished vascular NO availability.

The Spatial Distribution of Absolute Skeletal Muscle Deoxygenation During Ramp-Incremental Exercise Is Not Influenced by Hypoxia

“…Evidence in humans showing NOS inhibition impairs forearm vasodilation during exercise to a greater degree in hypoxia compared to normoxia supports this notion [5]. However, whether hypoxia decreases or increases NO remains controversial [3,5]. Exercise intensity is also known to alter blood flow spatial distribution in quadriceps muscles [6], with higher compared to lower power output associated with a more heterogeneous response.…”

“…This suggests that a narrow spatial distribution in Q O2/V O2 may reflect conditions detrimental to high rates of aerobic energy transfer. While the mechanisms matching regional Q O2 to V O2 remain equivocal, hypoxia may reduce nitric oxide (NO) bioavailability (a potent vasodilator) and limit the ability to maintain muscle regions with a high Q O2/V O2 ratio [3].…”

Effects of nitrite infusion on skeletal muscle vascular control during exercise in rats with chronic heart failure

“…CHFinduced vascular dysregulation is thought to be due, in part, to reduced nitric oxide (NO)-mediated function (Ref. 20; for a review, see Ref. 47).…”

“…VC was then calculated by normalizing BF to MAP measured at the time of microsphere infusion and expressed as ml·min Ϫ1 ·100 g tissue Ϫ1 ·mmHg Ϫ1 . The LV, right ventricle, and lungs were normalized to body weight, and MI size of the LV was measured via planimetry as previously described by our laboratory (20).…”

“…Although exercise rehabilitation represents an effective therapeutic modality for treating CHF (9), reduced NO bioavailability in CHF is associated with an impaired ability to perform exercise and/or even complete daily physical activities. Consequently, interventions that increase NO bioavailability may ameliorate the skeletal muscle vascular dysfunction evident in this disease (20,25) and thus have great potential to improve exercise tolerance and quality of life in this population.NO is synthesized endogenously via three isoforms of NO synthase (NOS) as well as by the nonenzymatic reduction of NO 3 Ϫ to NO 2 Ϫ and, finally, to NO (for a review, see Ref. 38).…”