Abnormalities in the regional circulations accompanying congestive heart failure

Zelis, Robert; Nellis, S. H.; Longhurst, John C.; Lee, Garrett; Mason, Dean T.

doi:10.1016/0033-0620(75)90010-9

Cited by 115 publications

(38 citation statements)

References 49 publications

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“…Also unexpected was ␣1A͞C expression in skin arterioles. Study of skin vessels by classical AR localization techniques is difficult because of their small size, but the skin accounts for Ϸ9% of resting cardiac output, and thus contributes significantly to vascular resistance (16). Further, localization of the ␣1A͞C in skin arteries indicates a potential role for this subtype in heat regulation, a common problem in diseases with abnormal sympathetic activity (16).…”

Section: Discussionmentioning

confidence: 99%

“…The skin, gut, and kidney together receive over 50% of resting cardiac output (16), and thus vasoconstriction in these beds is expected to have a major effect on blood pressure. Indeed, we showed that the ␣1A͞C-selective agonist A61603 caused a substantial hypertensive effect in WT and Het mice, and no effect in KO mice.…”

Section: Discussionmentioning

confidence: 99%

“…These results suggested that the ␣1A͞C was expressed normally in the gut, renal, and skin circulations. These vascular beds have major roles in blood pressure control (16).…”

Section: Generation and Confirmation Of The ␣1a͞c-ar Komentioning

confidence: 99%

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Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Rokosh

Simpson

2002

Proc. Natl. Acad. Sci. U.S.A.

181

185

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␣1-adrenergic receptors (ARs) play a major role in blood pressure regulation. The three ␣1-AR subtypes (A͞C, B, and D) stimulate contraction of isolated arteries, but it is uncertain how different subtypes contribute to blood pressure regulation in the intact animal. We studied the role of the ␣1A͞C subtype by using gene knockout. ␣1A͞C knockout (KO) mice were viable and overtly normal. The LacZ reporter gene replaced ␣1A͞C coding sequence in the KO, and ␤-galactosidase staining was present in resistance arteries and arterioles, but not in the thoracic aorta or its main branches. By tail cuff manometer and arterial catheter in conscious mice, ␣1A͞C KO mice were hypotensive at rest, with an 8 -12% reduction of blood pressure dependent on ␣1A͞C gene copy number. A61603, an ␣1A͞C-selective agonist, caused a pressor response that was lost in the KO and reduced but significant in heterozygous mice with a single copy of the ␣1A͞C. A subtype-nonselective agonist [phenylephrine (PE)] caused a pressor response in KO mice, but the final arterial pressure was only 85% of wild type. The baroreflex was reset in the KO, and heart rate variability was decreased. After baroreflex blockade with atropine, PE increased blood pressure but did not change heart rate. Cardiac and vascular responses to the ␤-AR agonist isoproterenol were unchanged, and the arterial lumen area was not altered. We conclude that the ␣1A͞C-AR subtype is a vasopressor expressed in resistance arteries and is required for normal arterial blood pressure regulation. ␣1A͞C-selective antagonists might be desirable antihypertensive agents.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Rokosh

Simpson

2002

Proc. Natl. Acad. Sci. U.S.A.

181

185

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“…This redistribution of limited cardiac output favours vital organs (i.e. heart and brain) over the liver, limbs, skeletal muscles and skin [4,5]. These adaptations, together with medications, sustain the compensated state of CHF.…”

Section: Compensatory Mechanisms In Chronic Heart Failurementioning

confidence: 99%

“…In advanced CHF, the reduction in resting cardiac output is accompanied by marked redistribution of the forward flow to regional circulations [4,5]. This redistribution of limited cardiac output favours vital organs (i.e.…”

Section: Compensatory Mechanisms In Chronic Heart Failurementioning

confidence: 99%

Acute heart failure as “acute endothelitis” — Interaction of fluid overload and endothelial dysfunction

Colombo

Onat

Sabbah

2008

European J of Heart Fail

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Positive inotropic effect of coenzyme Q₁₀, omega‐3 fatty acids and propionyl‐L‐carnitine on papillary muscle force‐frequency responses of BIO TO‐2 cardiomyopathic Syrian hamsters

et al. 2008

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The inability of heart muscle to generate ventricular pressure to adequately propel blood through the cardiovascular system is a primary defect associated with congestive heart failure (CHF). Force-frequency relationship (FFR) is one of the main cardiac defects associated with congestive heart failure. Thus FFR is a convenient methodological tool for evaluating the severity of muscle contractile dysfunction and the effectiveness of therapeutic agents. Papillary muscle isolated from BIO TO-2 cardiomyopathic Syrian hamsters (CMSHs), show a depressed FFR and represents an animal model of human idiopathic dilated cardiomyopathy. In the present study we investigated the effect of CoQ10, omega-3 fatty acids, propionyl-L-carnitine (PLC) and a combination of these 3 agents (formulation HS12607) on FFR in 8 month old BIO TO-2 CMSHs. Papillary muscles isolated from the anesthetized animals were placed in an incubation bath and attached to an isometric force transducer. A digital computer with an analog/digital interface allowed control of both muscle developed force and electrical stimulus parameters. Force-frequency response was evaluated, at Lmax, with increasing frequencies: 0.06, 0.12, 0.25, 0.5, 1, 2 and 4 Hz. HS12607-treatment produced a positive inotropic effect resulting in a significant enhancement (p < 0.05) of the peak force at the highest frequencies (1-4 Hz). In the range of frequency of 1-4 Hz also CoQ10 and omega-3 significantly (p < 0.05) attenuated the fractional decline in developed force. The significant improvement (p < 0.05) of the timing parameter peak rate of tension rise (+ T') and peak rate of tension fall (-T') indicating a faster rate of muscle contraction and relaxation respectively, found in CoQ10, omega-3 and PLC-treated CMSHs, may be due to the positive effects of these substances on sarcoplasmic reticulum functions. These findings suggest that naturally occurring CoQ10, omega-3 and PLC, particularly when administered together in a coformulation, might be a valid adjuvant to conventional therapy in dilated cardiomyopathy especially when considering that they are natural substances, devoid of side effects.

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Abnormalities in the regional circulations accompanying congestive heart failure

Cited by 115 publications

References 49 publications

Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Acute heart failure as “acute endothelitis” — Interaction of fluid overload and endothelial dysfunction

Positive inotropic effect of coenzyme Q₁₀, omega‐3 fatty acids and propionyl‐L‐carnitine on papillary muscle force‐frequency responses of BIO TO‐2 cardiomyopathic Syrian hamsters

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Abnormalities in the regional circulations accompanying congestive heart failure

Cited by 115 publications

References 49 publications

Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Knockout of the α1A/C-adrenergic receptor subtype: The α1A/C is expressed in resistance arteries and is required to maintain arterial blood pressure

Acute heart failure as “acute endothelitis” — Interaction of fluid overload and endothelial dysfunction

Positive inotropic effect of coenzyme Q10, omega‐3 fatty acids and propionyl‐L‐carnitine on papillary muscle force‐frequency responses of BIO TO‐2 cardiomyopathic Syrian hamsters

Contact Info

Product

Resources

About

Positive inotropic effect of coenzyme Q₁₀, omega‐3 fatty acids and propionyl‐L‐carnitine on papillary muscle force‐frequency responses of BIO TO‐2 cardiomyopathic Syrian hamsters