Desensitization of the pulmonary adenylyl cyclase system

Borst, Mathias M.; Beuthien, Wilke; Schwencke, Carsten; Rosée, Paul La; Marquetant, Rainer; Haass, Markus; Kübler, W.; Strasser, Ruth H.

doi:10.1016/s0735-1097(99)00251-x

Cited by 19 publications

(2 citation statements)

References 31 publications

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“…Indeed, in clinical practice it is often observed that patients with severe HF lack pulmonary rales on examination or alveolar edema on chest x-ray. Theoretically, the increase in pulmonary capillary hydrostatic pressure and wall tension due to the rise in LV filling pressure consistent with a failing LV (1) combined with down-regulation of the β receptors that are central to lung fluid removal mechanisms (2–4) secondary to a chronic increase in adrenergic drive should serve to make HF patients more susceptible to lung fluid accumulation relative to their healthy counterparts. However, it has also been shown that pulmonary microvascular permeability is decreased in severe HF patients, which would be expected to protect such patients from pulmonary edema (24).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, it has been shown that a chronic increase in adrenergic drive, as occurs with HF, elicits a down-regulation of the β receptors central to lung fluid removal mechanisms (2–4). In combination, it is possible that the aforementioned changes in the pulmonary system associated with HF may conspire to increase fluid flux across the pulmonary vasculature while impairing fluid clearance from the alveoli and interstitial space, thus making HF patients more susceptible lung fluid accumulation relative to their healthy counterparts.…”

Section: Introductionmentioning

confidence: 99%

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Effect of β 2 -adrenergic receptor stimulation on lung fluid in stable heart failure patients

Taylor

Snyder

Richert

et al. 2017

The Journal of Heart and Lung Transplantation

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Introduction The purpose of this study was to determine 1) if stable heart-failure patients with reduced ejection fraction (HFrEF) have elevated extravascular lung water (EVLW) versus healthy control subjects, and 2) the effect of acute β2AR agonist inhalation on lung fluid balance. Methods Twenty-two stable HFrEF patients and 18 age- and sex-matched healthy subjects were studied. Lung diffusing capacity for carbon monoxide (DLCO), alveolar-capillary conductance (DmCO), pulmonary capillary blood volume (Vc) (via rebreathe) and lung tissue volume (Vtis) (via computed tomography) were assessed before and within 30 min of administration of nebulized albuterol. EVLW was derived as Vtis – Vc. Results Pre-albuterol, Vtis and EVLW were greater in HFrEF vs. control (998 ± 200 vs. 884 ± 123 ml, P = 0.041; 943 ± 202 vs. 802 ± 133 ml, P = 0.015, respectively). Albuterol decreased Vtis and EVLW in HFrEF (−4.6 ± 7.8%, P = 0.010; −4.6 ± 8.8%, P = 0.018) and control (−2.8 ± 4.9%, P = 0.029; −3.0 ± 5.7%, P = 0.045). There was an inverse relationship between pre-albuterol values and the pre- to post-albuterol change for EVLW (r2 = −0.264, P = 0.015) and DmCO (r2 = −0.343, P = 0.004) in HFrEF only. Conclusion Lung fluid is elevated in stable HFrEF patients relative to healthy subjects. Stimulation of the β2ARs may cause fluid removal in HFrEF, especially in patients who exhibit greater evidence for increased lung water at baseline.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of β 2 -adrenergic receptor stimulation on lung fluid in stable heart failure patients

Taylor

Snyder

Richert

et al. 2017

The Journal of Heart and Lung Transplantation

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The Neuronal Norepinephrine Transporter in Experimental Heart Failure: Evidence for a Posttranscriptional Downregulation

Backs¹,

Haunstetter²,

Gerber³

et al. 2001

Journal of Molecular and Cellular Cardiology

102

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Central hypercapnic chemoreflex modulation of renal sympathetic nerve activity in experimental heart failure

et al. 2002

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Activation of the sympathetic nervous system plays an important role in the pathophysiology and progression of congestive heart failure (CHF). The precise mechanisms responsible for sympathetic activation in CHF are not yet clearly established. An altered central hypercapnic chemoreflex modulation of sympathetic nerve activity (SNA) might be an explanation. Therefore, the response of postganglionic renal SNA to elevation of CO2 concentration in the inspiratory air to 2, 4, and 6% was determined in anesthetized, artificially ventilated rats after denervation of peripheral baro- and chemoreceptors 2 weeks (group A; n=8) or 6 weeks (group B; n=11) after induction of an aorto-caval shunt, or 4 weeks after aortic banding (group C; n=7). In all CHF models, left ventricular enddiastolic pressure was increased (A 8 +/- 1, B 8 +/- 1, C 10 +/- 2 mmHg) as compared to sham operated controls (A 3 +/- 1, B 4 +/- 1, C 5 +/- 1 mmHg). Indicative of left ventricular hypertrophy and pulmonary congestion, wet weight of heart (A + 60%, B + 93%, C + 49%) and lungs (A + 15%, B + 36%, C + 12%) were also enhanced as compared to controls. Elevation of inspiratory CO2 concentration to 2,4, and 6% increased renal SNA by approximately 10, 20, and 30% from resting activity in all groups. The maximum SNA responses at 6% CO2 in the groups with CHF (A + 390 +/- 95, B + 425 +/- 133, C + 368 +/- 158 microVs) did not differ from those in the respective controls (A + 510 +/- 130, B + 570 +/- 180, C + 275 +/- 25 microVs). It is concluded that under these experimental conditions the central hypercapnic chemoreflex sensitivity is not altered in either of the employed models of CHF and therefore may not play a major role for the well-known elevation of SNA in CHF.

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Desensitization of the pulmonary adenylyl cyclase system

Abstract: In heart failure, the down-regulation of pulmonary beta-receptors and concomitant decrease in adenylyl cyclase activity result in a significant attenuation of cAMP-mediated airway relaxation. These mechanisms may play a pivotal role in the pathogenesis of"cardiac asthma."

Cited by 19 publications

References 31 publications

Effect of β 2 -adrenergic receptor stimulation on lung fluid in stable heart failure patients

Effect of β 2 -adrenergic receptor stimulation on lung fluid in stable heart failure patients

The Neuronal Norepinephrine Transporter in Experimental Heart Failure: Evidence for a Posttranscriptional Downregulation

Central hypercapnic chemoreflex modulation of renal sympathetic nerve activity in experimental heart failure

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