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Long-term exercise training and angiotensin-converting enzyme inhibition differentially enhance myocardial capillarization in the spontaneously hypertensive rat.

OBJECTIVES: To investigate whether combined treatment with lisinopril, an angiotensin-converting enzyme (ACE) inhibitor and exercise training would have an additive effect in enhancing the capillary supply of the left ventricular (LV) myocardium in spontaneously hypertensive rats (SHR). DESIGN: Twelve-week-old male SHR were divided into four groups (10-12 each): sedentary, sedentary treated with lisinopril (15-20 mg/kg per day by gavage), exercise trained, and exercise trained while treated with lisinopril. Exercise training consisted of 1 h a day/5 days a week of running on a treadmill. METHODS: After 10 weeks of experimental protocols, capillary surface density and length density were sterologically determined in 1 mum thick LV tissue samples from perfuse-fixed hearts. RESULTS: Lisinopril significantly reduced systolic blood pressure (SBP) and LV mass in the sedentary with lisinopril and exercise trained with lisinopril groups but did not affect the heart rate (HR). Exercise training did not reduce SBP or LV mass, but significantly reduced HR in the exercise trained and exercise trained with lisinopril groups. Lisinopril treatment (sedentary with lisinopril), exercise training (exercise) and their combination (exercise trained with lisinopril) significantly increased myocardial capillary surface area density by 26, 38 and 65% and length density by 38, 48 and 67%, respectively. CONCLUSION: Lisinopril administration and exercise training independently enhanced myocardial capillarization through a reduction of myocardial mass and stimulation of angiogenesis, respectively. A combination of the two treatments enhanced myocardial capillarization more than either intervention alone. This may aid in the restoration of the normal nutritional status of cardiac myocytes compromised by the hypertrophic state of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Implications for connective tissue and bone alterations resulting from resistance exercise training.

Few studies have addressed the effects of resistance training on connective tissue. Inferences from studies investigating the effects of endurance training or "loaded" exercise training can be made. The available data suggest that 1) physical activity can increase connective tissue strength and mass, 2) activation of the antigravity muscles must be accomplished to adequately stimulate connective tissue, and 3) the volume, intensity, and load-bearing nature of the exercise training are important factors in causing connective tissue adaptations. Based on the above factors, a speculative model of training for increased maximum strength of connective tissue has been developed.

Adaptation, Physiological↗

Supervised versus unsupervised exercise training following myocardial infarction and myocardial revascularisation procedures.

Exercise training is an important component of rehabilitative care for patients following myocardial infarction or myocardial revascularisation procedures. Participation of the patient in supervised exercise training, however, is not always practical, and home exercise training may be a reasonable alternative for low-risk patients. The relatively routine predischarge exercise test, performed for risk stratification, can identify low-risk patients and guide their exercise prescription during the early weeks at home. Advantages of home exercise training include increased availability and convenience and lower cost. Comparable improvements in functional capacity have been documented to result from home exercise and supervised group programmes. Drawbacks, however, involved the limited ability to teach patients the necessary safety precautions for exercise, the lack of opportunity to teach and encourage modification of coronary risk-related behaviours and lifestyles, and the lack of peer support. Several techniques have been proposed to overcome some limitations of home exercise and to encourage long-term adherence to the exercise regimen. Among these are telephone interaction between patients and nurses or other health professionals, transtelephonic exercise ECG recording, and the use of home exercise training videocassette. Comparative studies of the safety, efficacy, and costs of these approaches are needed; and means must be devised to provide the nonexercise-related information and counselling available to coronary patients in a supervised exercise setting.

Electrocardiography, Ambulatory↗

Effect of low-intensity aerobic exercise training on arterial compliance in postmenopausal women.

Regular aerobic exercise training attenuates age-related reduction in central arterial compliance, an independent risk factor of cardiovascular diseases. We tested the hypothesis that even low-intensity exercise training could increase central arterial compliance in postmenopausal women. Using B-mode ultrasound, we studied the central arterial compliance of 15 postmenopausal females (age: 52-66 years) before and after a 12-week aerobic exercise intervention. Subjects performed aerobic exercise training of the same energy expenditure (cycle exercise, total 900 kcal/week, 3-5 sessions/week) at two different exercise intensities: 7 trained at low intensity (40% heart rate reserve: L-TR) and 8 trained at moderate intensity (70% heart rate reserve: M-TR). Arterial compliance increased after exercise training in the L-TR group (0.70+/-0.32 vs. 1.06+/-0.55 mm2/mmHgX10(-1), p <0.05) and in the M-TR group (0.82+/-0.37 vs. 1.14+/-0.39 mm2/mmHgX10(-1), p <0.05). There was no significant difference in increases of arterial compliance in either group (L-TR: 0.35+/-0.38 vs. M-TR: 0.32+/-0.33 mm2/mmHgX10(-1)). These results suggest that the improvement of central arterial compliance by aerobic exercise training might not be influenced by the intensity of exercise training if the energy expenditure of the training is the same. Accordingly, even low-intensity exercise training may have the effect of improving central arterial compliance.

Carotid Arteries↗

Exercise training in obesity lowers blood pressure independent of weight change.

PURPOSE: We used the rabbit model of obesity and exercise training to determine effects of exercise training during the development of obesity on resting blood pressure and heart rate, ventricular hypertrophy, blood volume, and hormonal profile. METHODS: Female New Zealand white rabbits were assigned to one of four groups: lean sedentary (L-S, N = 17), lean exercise-trained (L-EX, N = 16), obese sedentary (O-S, N = 18), and obese exercise-trained (O-EX, N = 15). Lean rabbits were fed a maintenance diet whereas obese rabbits were fed an ad libitum high fat (10% added fat) diet. Simultaneously, exercise-trained animals underwent a progressive treadmill exercise training protocol for 12 wk. After 12 wk of diet and exercise regimens, resting blood pressure and heart rate were measured from a central ear artery catheter. Ventricular hypertrophy was evaluated using wet ventricular weights. Blood volume was measured using the Evans blue dye procedure; hormonal profile was evaluated from arterial plasma/serum samples. RESULTS: After 12 wk, O-S and O-EX had similar body weights and similar percentage increases in body weight. Despite similar body weights, O-EX had an approximate 6-mm Hg lower mean blood pressure compared with the elevated pressure seen in O-S (P < or = 0.05). Obese rabbits had greater resting heart rate, plasma cholesterol and triglycerides, and plasma renin activity compared with lean rabbits, and these values were unaffected by exercise training. Plasma and blood volumes, as well as plasma insulin, cortisol, and aldosterone were unaffected by exercise training. CONCLUSION: These data suggest that exercise training, in the absence of differences in body weight, may be useful in the reduction of obesity-induced hypertension but that other therapies may be needed in order to control other cardiovascular risk factors.

Animals↗

Novel quantitative phenotypes of exercise training in mouse models.

Regular physical exercise has beneficial effects in many human disease states, including cardiovascular diseases, cancer, and depression. Exercise training of genetically modified mouse models may provide insight into the molecular mechanisms that underlie the beneficial effects of exercise. Presently, there is relatively little understanding of the normal physiology of mouse exercise. In this paper, we describe a novel computerized voluntary wheel-running system capable of recording and analyzing individual wheel rotations. Using this system, we demonstrate that C57BL/6 mice run considerable distances during the night in short bouts and at a preferred speed: the cruising speed. We find that the vast majority of running occurs around this cruising speed, which is close to the maximum speed at which the animal can run but is significantly higher than the average speeds recorded by simple digital odometers. We describe how these parameters vary with exercise training and demonstrate marked sex differences in the patterns of voluntary exercise. The results of this study have important implications for the design and interpretation of both voluntary and forced exercise experiments in mouse models. The novel parameters described provide more physiological quantitative measures of voluntary exercise activity and training and will extend the physiological utility of exercise training as a phenotyping tool in genetic mouse models.

Animals↗

Effects of adenosine and pertussis toxin on lipolysis in adipocytes from exercise-trained male rats.

The sensitivity and responsiveness of adipocyte lipolysis to adenosine and pertussis toxin were studied in exercise-trained male rats. Exercise training (9 weeks of treadmill running) significantly increased lipolytic response of adipocytes to noradrenaline (NA). Addition of adenosine deaminase (ADA) to reaction mixture effectively enhanced NA-stimulated lipolysis in adipocytes from both conditioned rats. However, under these conditions, the difference due to exercise training was still evident, although the difference was less pronounced. The inhibition curves of the R-site adenosine analogue N6-phenylisopropyladenosine (PIA) against "basal" (lipolysis in the presence of ADA) and NA-stimulated lipolysis were almost comparable between two groups. Only a small (approx. 2-fold) increase in IC50 of adipocyte lipolysis was observed in each inhibition curve in exercise-trained rats. Within 120 min of addition of pertussis toxin to adipocytes from control rats, "basal" lipolysis was significantly increased as compared to "basal" lipolysis in the absence of toxin at the same point. Similarly, pertussis toxin significantly increased "basal" lipolysis in exercise-trained adipocytes. However these were relatively sensitive to pertussis toxin, since significant effect of toxin was seen within 60 min. An addition of NA (0.1 uM) to the medium in the presence of ADA and toxin significantly increased adipocyte lipolysis in both conditioned rats. Again, under these conditions, we observed that the maximal rate of lipolysis of adipocytes from exercise-trained rats was increased as compared to control rats. These results suggest that the decreased input through the inhibitory pathway in lipolytic cascade may be not rate limiting for the amplified lipolytic responsiveness of adipocytes to hormonal stimuli in exercise-trained rats.

Adenosine↗

Attenuation of endothelial dysfunction by exercise training in STZ-induced diabetic rats.

The protective effects of exercise training on the diabetic-induced endothelial cell (EC) dysfunction were determined using intravital fluorescent microscopy. Male Sprague-Dawley rats were divided into three groups of control (Con), diabetes (DM), and diabetes with exercise--training (DM+Ex). Diabetes was induced by single intravenous injection of streptozotocin (STZ; 50 mg/kg BW). The exercise training protocol consisted of treadmill running, 5 times/week with the velocity of 13-15 m/min, 30 min/day periods for 12 and 24 weeks (wks). 24 wks after the STZ injection, blood glucose (BG), glycosylated hemoglobin (HbA1C), mean arterial blood pressure (MAP) and heart weight (HW) were significantly higher in DM rats (p < 0.001). However, DM+Ex rats had reduced the abnormalities of MAP (p < 0.01) and HW (p < 0.05) compared with DM rats. Furthermore, there was a significant decrease in heart rate (HR) of DM+Ex rats (p < 0.05) relative to Con rats. To examine the influence of exercise training on EC dysfunction, leukocyte-EC interactions in mesenteric venules and vascular reactivity responses to vasodilators in mesenteric arterioles were monitored by using intravital fluorescence microscopy. The diabetic state enhanced leukocyte adhesion in mesenteric postcapillary venules (p < 0.001). Moreover, an impaired vasodilatory response to the EC-dependent vasodilator, acetylcholine (Ach), not to sodium nitroprusside (SNP), was found in 12- and 24-wk diabetic rats (p < 0.01). The leukocyte adhesion and the impairment of EC-dependent vasodilation to Ach were attenuated by exercise training (p < 0.05). In addition, exercise training was also shown to have favorable preventive effects on hyperglycemia induced oxidative stress, as lower malondialdehyde (MDA) levels were observed from both groups of 12 and 24 weeks DM+Ex compared with DM (p < 0.01). In conclusion, our findings indicate that the endothelial dysfunction of diabetic rats could be characterized by increased leukocyte adhesion and impaired endothelium-dependent relaxation. Regular low intensity exercise training could improve both indices of endothelial dysfunction through amelioration of diabetic-induced oxidant/antioxidant levels. These findings support the notion that regular exercise training could be a fundamental form of therapy in preventing diabetic cardiovascular complications potentiated by endothelial dysfunction.

Acetylcholine↗

High versus low intensity exercise training in pulmonary rehabilitation: is more better?

BACKGROUND: Exercise training is considered a necessary component of comprehensive pulmonary rehabilitation. However, to date, there is no consensus on an exercise training strategy for pulmonary rehabilitation, and this has resulted in varied approaches to this intervention in its literature. As in healthy individuals, the effect of exercise training on patients with chronic lung disease is dose dependent, with higher intensities resulting in greater physiological adaptations than lower intensities. RESULTS: It is not clear from our review of the literature that these enhanced physiological effects from higher levels of exercise training translate into a reduced burden of symptoms, hence a better quality of life. Indeed, there is some evidence that pulmonary rehabilitation approaches incorporating lower intensities of exercise training are at least as good in improving questionnaire rated symptoms of health status. This provides food for thought, since the prominent goal of pulmonary rehabilitation should be to reduce bothersome symptoms or enhance health status, not simply increase endurance time on a cycle ergometer.

Exercise Therapy↗

Responses of antioxidant system to acute and trained exercise in rat heart subcellular fractions.

The effects of acute and trained exercise on antioxidant enzymes (AOE), glutathione (GSH), and malondialdehyde (MDA) were compared in rat heart subcellular fractions and red blood cells. Fischer-344 rats were exercised acutely to 100% VO2 max and another group of Fischer-344 rats were given trained exercise for 10 weeks. The AOE and MDA were measured by spectrophotometry and GSH and oxidized GSH (GSSG) by high pressure liquid chromatography. Trained exercise significantly increased cytosol GSH to 131% of sedentary control (SC). Acute exercise significantly increased mitochondrial superoxide dismutase, catalase, and glutathione peroxidase by 167%, 358%, and 129% of SC, respectively, whereas enzyme activities following trained exercise were increased by 133%, 166%, and 128% of SC. The mitochondria/cytosolic ratio for superoxide dismutase, catalase, and glutathione peroxidase after acute exercise increased to 1.9, 2.7, and 1.7, respectively, whereas the respective ratios of these enzymes after trained exercise were 1.3, 1.6, and 1.3. Acute exercise contributed to oxidative stress more than trained exercise. Acute exercise resulted in a larger increase in enzyme activities than trained exercise, possibly as a compensatory mechanism to cope with the enhanced production of superoxides and oxyradicals during exhaustive exercise.

Animals↗

Endurance exercise training attenuates leucine oxidation and BCOAD activation during exercise in humans.

We studied the effects of a 38-day endurance exercise training program on leucine turnover and substrate metabolism during a 90-min exercise bout at 60% peak O(2) consumption (VO(2 peak)) in 6 males and 6 females. Subjects were studied at both the same absolute (ABS) and relative (REL) exercise intensities posttraining. Training resulted in a significant increase in whole body VO(2 peak) and skeletal muscle citrate synthase (CS; P < 0.001), complex I-III (P < 0.05), and total branched-chain 2-oxoacid dehydrogenase (BCOAD; P < 0.001) activities. Leucine oxidation increased during exercise for the pretraining trial (PRE, P < 0.001); however, there was no increase for either the ABS or REL posttraining trial. Leucine oxidation was significantly lower for females at all time points during rest and exercise (P < 0.01). The percentage of BCOAD in the activated state was significantly increased after exercise for both the PRE and REL exercise trials, with the increase in PRE being greater (P < 0.001) compared with REL (P < 0.05). Females oxidized proportionately more lipid and less carbohydrate during exercise compared with males. In conclusion, we found that 38 days of endurance exercise training significantly attenuated both leucine oxidation and BCOAD activation during 90 min of endurance exercise at 60% VO(2 peak) for both ABS and REL exercise intensities. Furthermore, females oxidize proportionately more lipid and less carbohydrate compared with males during endurance exercise.

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

Safety and effectiveness of exercise training in patients with silent myocardial ischemia.

The effectiveness of exercise training in patients with silent myocardial ischemia was examined. Forty patients with coronary heart disease (mean age 55 +/- 8 years) were recruited for a 12-week exercise training program. All patients underwent treadmill exercise stress testing, exercise thallium-201 single photon emission computed tomography and left heart catheterization. They were divided into three groups based on the symptoms and the results of exercise thallium scintigraphy, i.e., painful myocardial ischemia (PMI group), silent myocardial ischemia (SMI group), and non-myocardial ischemia (NMI group). Normalized treadmill time was longer in the SMI group (108 +/- 24%) than in the PMI group (86 +/- 14%, p < 0.05). All 40 patients, 14 from the PMI group, 16 from the SMI group and 10 from the NMI group, completed the whole exercise training program. A significant prolongation of treadmill time was attained in all three groups after exercise training [PMI group: from 494 +/- 105 to 632 +/- 78 sec (p < 0.05), SMI group: from 609 +/- 147 to 746 +/- 137 sec (p < 0.05), NMI group: from 572 +/- 112 to 739 +/- 13 sec (p < 0.05)]. The improvement of myocardial ischemia following exercise training was similar in the SMI and PMI groups. No adverse effects were detected throughout the program. The exercise training program adopted in this study proved safe and effective in patients with silent myocardial ischemia.

Adult↗

Lipoprotein lipase in adipose tissues of exercise-trained, cold-acclimated rats.

The combined effects of exercise training and cold acclimation on serum lipids and on the activity of lipoprotein lipase (LPL) in epididymal white (WAT) and interscapular brown adipose tissues (BAT) of the rat were evaluated. Sedentary and exercise-trained (treadmill) rats were housed and trained at either 24 or 4 degrees C for 45 days. Although neither treatment given alone influenced serum total cholesterol, exercise training in the cold resulted in a 54% increase in this variable. Serum triglycerides were lowered to 80% of control values by exercise training and to 44% of control by cold acclimation. Both treatments resulted in lower insulin and thyroxine concentrations, while triiodothyronine levels were unaffected. Total LPL activity in WAT was increased twofold by exercise training at both temperatures, whereas cold acclimation stimulated WAT LPL activity to a lesser extent. Exercise training had no overall effect on LPL activity of BAT, whereas cold acclimation increased the latter in both sedentary (217%) and trained (420%) animals. These results emphasize the potential importance of LPL-mediated lipid assimilation in the metabolic events that lead to energy production in response to environmental stresses and lend support to the notion that the regulation of LPL activity is tissue specific.

Acclimatization↗

[Exercise training in cardiac patients: usefulness of the cardiopulmonary exercise test].

Exercise training is currently including in the treatment of coronary arterial disease patients, in patients with left ventricular dysfunction as well as in patients who underwent cardiac transplantation or cardiac surgery. However methods of prescribing exercise-training programs are difficult to determine and must be adapted for each patient Exercise test with gas analysis through the determination of anaerobic threshold may help to understand the physiopathological mechanism related to exercise limitation in these patients. Exercise test may help to precise exercise intensity during cardiac rehabilitation and may assess the benefits on exercise tolerance.

Exercise Test↗

Changes in insulin response to glucose after exercise training in partially pancreatectomized rats.

The effects of exercise training on glucose-stimulated insulin secretion (GSIS) were studied in male Sprague-Dawley rats made mildly to severely diabetic by partial pancreatectomy. Exercise trained (10 wk treadmill; T) and untrained (Unt) rats were grouped according to posttraining fed-state hyperglycemia as follows: T less than 200 and Unt less than 200 (glucose concn less than 200 mg/dl), T 200-300 and Unt 200-300 (glucose concn 200-300 mg/dl), and T greater than 300 and Unt greater than 300 (glucose concn greater than 300 mg/dl). After exercise training, hyperglycemic glucose clamps were performed in awake rats by elevation of arterial blood glucose concentration 126 mg/dl above fasting basal levels for 90 min. Exercise training significantly increased muscle citrate synthase activity. Prevailing hyperglycemia was reduced during the 10-wk exercise training period in all T rats with fed-state glucose concentrations less than 300, and only 53% of Unt rats in these groups had reduced glycemia. GSIS was significantly higher in T less than 200 [2.4 +/- 0.7 (SD) ng/ml at 90 min] than in Unt less than 200 (1.5 +/- 0.3). A similar response was found for T 200-300 (1.1 +/- 0.3 ng/dl) vs. Unt 200-300 (0.7 +/- 0.1) but not T greater than 300 (0.36 +/- 0.2) vs Unt greater than 300 (0.44 +/- 0.05). Sham-operated control rats had insulin concentrations of 6.6 +/- 1.6 ng/ml at the 90th min of the clamp. Acute exercise reduced fed-state glycemia in rats with mild-to-moderate (less than 300 mg/dl) diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The importance of exercise training in rehabilitation of patients with end-stage renal disease.

Exercise capacity in patients with kidney failure undergoing dialysis is low compared with age-predicted values. The level of exercise tolerance in these patients is such that the energy requirements for activities of daily living and occupational tasks impinge on their capacity to perform these tasks. Therefore, it is not surprising that many patients do not seek or are unable to work because they are physically unable to sustain the energy required for such activity. There are several ways to increase exercise tolerance in these patients--transplant, exercise training, and recombinant human erythropoietin (epoetin) therapy. Successful kidney transplant increases exercise capacity to near normal values for sedentary healthy individuals. Exercise training after transplant further increases exercise capacity and counteracts some of the negative side effects of glucocorticoid therapy, such as muscle wasting and excessive weight gain. Exercise training in patients on dialysis increases exercise tolerance approximately 25% (in studies performed before epoetin administration). Similar increases are observed after correction of the anemia of kidney failure with epoetin. However, the increase in exercise capacity is small compared with the magnitude of change in hematocrit level. It is possible that epoetin therapy unmasks a muscle limitation to exercise that may be improved by exercise training. Anecdotal evidence suggests that exercise training in patients on epoetin therapy may result in an exercise capacity similar to that of transplant recipients. However, epoetin therapy to improve hematocrit levels does not automatically make patients exercise. Active counseling and encouragement are necessary to improve physical functioning.(ABSTRACT TRUNCATED AT 250 WORDS)

Exercise↗

Effect of exercise training on the untrained limb exercise performance of men with angina pectoris.

This study examined the exercise capacity of trained and untrained limbs in men with angina pectoris before and after 8 weeks of arm ( n = 4) or leg (n = 7) physical training or a control (n = 4) period. Time to angina (mean +/- standard deviation) increased 3.6 +/- 2.7 minutes (p less than 0.01) during trained limb and 1.6 +/- 1.2 minutes (p less than 0.01) during untrained limb exercise. Myocardial oxygen demand at angina estimated by the product of heart rate and systolic blood pressure did not change with training. At a constant subanginal work load, rate-pressure product x 10(-2) was reduced by 35 +/- 22 (p less than 0.001) during trained limb and by 18 +/- 27 (p less than 0.05) during untrained limb exercise. The decrease in rate-pressure product with both trained and untrained limbs was greatest in subjects with the highest rate-pressure product at angina before training. Control subjects showed no change in any exercise measurement. Exercise training increases the exercise capacity of untrained limbs in patients with angina pectoris by a generalized training effect not dependent on adaptations in trained skeletal muscle. The improvement for both trained and untrained limbs results from a reduced rate-pressure product at subanginal work loads rather than from an increase in myocardial oxygen delivery. Subjects with the highest pretraining coronary arterial oxygen supply at the onset of angina benefit most from physical training.

Angina Pectoris↗

Exercise training increases basal tone in arterioles distal to chronic coronary occlusion.

Endurance exercise training increases basal active tone in coronary arteries and enhances myogenic tone in coronary arterioles of control animals. Paradoxically, exercise training has also been shown to augment nitric oxide production and nitric oxide-mediated relaxation in coronary arterioles. The purpose of the present study was to examine the effect of exercise training on basal active tone of arterioles (approximately 150 microm ID) isolated from the collateral-dependent region of hearts exposed to chronic coronary occlusion. Ameroid occluders were surgically placed around the proximal left circumflex coronary artery of miniature swine. Arterioles were isolated from both the collateral-dependent and nonoccluded myocardial regions of sedentary (pen confined) and exercise-trained (treadmill run; 14 wk) pigs. Coronary tone was studied in isolated arterioles using microvessel myographs and standard isometric techniques. Exposure to nominally Ca2+-free external solution reduced resting tension in all arterioles; decreases were most profound (P < 0.05) in arterioles from the collateral-dependent region of exercise-trained animals. Furthermore, nitric oxide synthase (NOS) inhibition (N(omega)-nitro-L-arginine methyl ester; 100 microM) unmasked markedly increased nitric oxide-sensitive tone in arterioles from the collateral-dependent region of exercise-trained swine. Blockade of K+ channels revealed significantly enhanced K+ channel contribution to basal tone in collateral-dependent arterioles of exercise-trained pigs. Protein content of endothelial NOS (eNOS) and phosphorylated eNOS (pS1179), determined by immunoblot, was elevated in arterioles from exercise-trained animals with the greatest effect in collateral-dependent vasculature. Taken together, we demonstrate the interaction of opposing exercise training-enhanced arteriolar basal active tone, nitric oxide production, and K+ channel activity in chronic coronary occlusion, potentially enhancing the capacity to regulate blood flow to collateral-dependent myocardium.

Animals↗