Increased Systolic Performance With Diastolic Dysfunction in Adult Spontaneously Hypertensive Rats

Cingolani, Oscar H.; Yang, Xiao Ping; Cavasin, Maria A.; Carretero, Oscar A.

doi:10.1161/01.hyp.0000052832.96564.0b

Cited by 111 publications

(121 citation statements)

References 41 publications

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“…This motivated us to study the effect of MMR on ventricular contractility not only with the ϩdP/dt max approach but also in the pressure-volume plane. Several investigators have demonstrated that the ESPVR, as well as its slope (maximal ventricular elastance), E max , is relatively insensitive under physiological conditions to changes in preload and afterload yet sensitive to changes to the contractile state of the ventricle (5,10,11,15,16,40). In the present study, we observed that from rest to mild exercise, dP/dt max rose significantly, yet this rise was Ͻ5%.…”

Section: Discussionsupporting

confidence: 45%

Muscle metaboreflex control of ventricular contractility during dynamic exercise

Sala‐Mercado¹,

Hammond²,

Kim³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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When oxygen delivery to active skeletal muscle is insufficient for the metabolic demands, afferent nerves within muscles are activated, which elicit reflex increases in heart rate (HR), cardiac output (CO), and arterial pressure (AP), termed the muscle metaboreflex (MMR). To what extent the increases in CO are the result of increased ventricular contractility is unclear. A widely accepted index of contractility is maximal left ventricular elastance (Emax), the slope of the end-systolic pressure-volume relationship, such as during rapidly imposed reductions in preload. The objective of the present study was to determine whether MMR activation elicits increases in Emax. Experiments were performed using conscious dogs chronically instrumented to measure left ventricular pressure and volume at rest and during mild or moderate treadmill exercise with and without partial hindlimb ischemia to elicit MMR responses. At both workloads, MMR activation significantly increased CO, HR, AP, and maximum rate of change of left ventricular pressure. During both mild and moderate exercise, MMR activation increased Emax to 159.6 Ϯ 8.83 and 155.8 Ϯ 6.32% of the exercise value under free-flow conditions, respectively. We conclude that the increase of ventricular elastance associated with MMR activation indicates that a substantial increase in ventricular contractility contributes to the rise in CO during dynamic exercise. elastance; pressor response; cardiac function DURING DYNAMIC EXERCISE, when oxygen delivery to active skeletal muscle is insufficient to meet the metabolic demands, metabolites (e.g., lactic acid, adenosine, potassium, diprotonated phosphate, H ϩ , arachidonic acid products, and others) accumulate within the active muscle and stimulate group III and IV afferent neurons. These sensory neurons project to the central nervous system, eliciting a reflex pressor response consisting of increases in efferent sympathetic nerve activity (SNA), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), plasma levels of vasoactive hormones, and peripheral vasoconstriction termed the muscle metaboreflex (MMR) (1, 2, 8, 12, 14, 19, 21, 25-28, 30, 32, 33, 35-38, 42, 44). These mechanisms act in concert to partially restore blood flow and arterial oxygen delivery to the hypoperfused muscles (27,31). Previous studies have shown that in normal dogs exercising at mild and moderate workloads, the increases in MAP elicited by this MMR activation are mainly due to increases in CO. The rise in CO likely results from increases in ventricular performance, HR, and central blood volume mobilization (26, 35). In this way the MMR-induced increases in ventricular performance act to sustain or slightly increase stroke volume (SV) despite decreases in ventricular filling time due to the reflex tachycardia (2, 26, 44). Furthermore, O'Leary an Augustyniak (26) showed that in normal dogs in which HR was fixed at 225 beats/min during mild exercise, MMR activation caused such a rise in SV that the increases in CO were approximately equal to t...

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Section: Discussionsupporting

confidence: 45%

Muscle metaboreflex control of ventricular contractility during dynamic exercise

Sala‐Mercado¹,

Hammond²,

Kim³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…Okayama et al (22) reported that relaxation was not altered in isolated myocytes of SHR at 10 weeks of age, but Nishimura et al (29) analyzed LV diastolic function using τ and demonstrated prolongation at 28 and 50 weeks of age compared with agematched WKY. In the same way, Cingolani et al (23) showed an increase in τ in adult SHR (10 to 11 months old) using a catheter pressure transducer. It is unclear when diastolic dysfunction develops in the SHR heart, but at 10 weeks of age the length and diameter of cardiomyocytes are larger than normal (22) and there is increased collagen content in the LV wall (32).…”

Section: Discussionmentioning

confidence: 71%

“…Other investigators found increased contractility in myocytes isolated from the SHR heart (21,22). Hemodynamic measurements using a catheter pressure transducer in vivo have shown increased systolic performance of SHR hearts (22,23). However, there have also been reports that contractility was not changed in these animals (24,25).…”

Section: Discussionmentioning

confidence: 98%

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

et al. 2005

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“…40 Blocking endocannabinoid inactivation reduces both the elevated arterial pressure and the increased LV contractile performance without affecting the same parameters in normotensive animals. This offers an innovative approach to the pharmacotherapy of hypertension by simultaneously targeting and normalizing the inappropriately increased LV contractile performance and vascular tone.…”

Section: Discussionmentioning

confidence: 99%

Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension

et al. 2004

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Background-Endocannabinoids are novel lipid mediators with hypotensive and cardiodepressor activity. Here, we examined the possible role of the endocannabinergic system in cardiovascular regulation in hypertension. Methods and Results-In spontaneously hypertensive rats (SHR), cannabinoid-1 receptor (CB 1 ) antagonists increase blood pressure and left ventricular contractile performance. Conversely, preventing the degradation of the endocannabinoid anandamide by an inhibitor of fatty acid amidohydrolase reduces blood pressure, cardiac contractility, and vascular resistance to levels in normotensive rats, and these effects are prevented by CB 1 antagonists. Similar changes are observed in 2 additional models of hypertension, whereas in normotensive control rats, the same parameters remain unaffected by any of these treatments. CB 1 agonists lower blood pressure much more in SHR than in normotensive Wistar-Kyoto rats, and the expression of CB 1 is increased in heart and aortic endothelium of SHR compared with Wistar-Kyoto rats. Conclusions-We conclude that endocannabinoids tonically suppress cardiac contractility in hypertension and that enhancing the CB 1 -mediated cardiodepressor and vasodilator effects of endogenous anandamide by blocking its hydrolysis can normalize blood pressure. Targeting the endocannabinoid system offers novel therapeutic strategies in the treatment of hypertension.

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Increased Systolic Performance With Diastolic Dysfunction in Adult Spontaneously Hypertensive Rats

Cited by 111 publications

References 41 publications

Muscle metaboreflex control of ventricular contractility during dynamic exercise

Muscle metaboreflex control of ventricular contractility during dynamic exercise

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

Endocannabinoids Acting at Cannabinoid-1 Receptors Regulate Cardiovascular Function in Hypertension

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