Effects of corticotropin-releasing factor on isolated rat heart activity

Grunt, M.; Glaser, Jacob; Schmidhuber, H.; Pauschinger, P.; Born, Jan

doi:10.1152/ajpheart.1993.264.4.h1124

Cited by 23 publications

(31 citation statements)

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“…Previous studies have demonstrated that coronary blood flow and aortic pressure changes during CRF perfusion of isolated rat hearts were not affected by cotreatment with propranolol (34). Our data support these findings in that pretreatment with the ␤-AR antagonist, esmalol, did not interfere with enhancement of peak (ϩ) dP͞dt by UcnII treatment of wild-type mice.…”

Section: Discussionsupporting

confidence: 89%

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Bale

Hoshijima

et al. 2004

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

120

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Corticotropin-releasing factor (CRF) and its paralogues urocortin (Ucn)I, -II, and -III signal by activating their receptors, CRF receptors (CRFR)1 and -2, to maintain homeostasis through endocrine, autonomic, and behavioral responses. CRFR2 is found in cardiomyocytes and in endothelial and smooth muscle cells of the systemic vasculature. Echocardiography and cardiac catheterization were used in mice to assess the physiologic effects of i.v. UcnII and CRFR2 deficiency on left ventricular function and the systemic vasculature. UcnII treatment augmented heart rate, exhibited potent inotropic and lusitropic actions on the left ventricle, and induced a downward shift of the diastolic pressure-volume relation. UcnII also reduced systemic arterial pressure, associated with a lowering of systemic arterial elastance (end-systolic pressure͞stroke volume) and systemic vascular resistance. CRFR2-deficient mice showed no alteration in cardiac contractility or blood pressure in response to UcnII administration, suggesting that the effects of UcnII are specific to CRFR2 function. Pretreatment with a ␤-adrenergic receptor antagonist, esmalol, had no effect on the inotropic or lusitropic effects of UcnII in vivo, indicating that its actions are independent of ␤-adrenergic receptors. Single i.v. bolus administration of UcnII to a heart failure model (muscle-specific LIM protein-deficient mice) produced significant enhancement of inotropic and lusitropic effects on left ventricular function and improved cardiac output. These results demonstrate the potent cardiovascular physiologic actions of UcnII in both wild-type and cardiomyopathic mice and support a potential beneficial use of this peptide in therapy of congestive heart failure.corticotropin-releasing factor receptor 2 ͉ hemodynamics ͉ inotropic agents ͉ lusitropic agents ͉ afterload reduction C orticotropin-releasing factor (CRF), a coordinator of the hypothalamic-pituitary-adrenal axis (1), is one of a family of peptides that includes urocortin (Ucn)I (2), UcnII (also known as stresscopin-related peptide) (3, 4), and UcnIII (also known as stresscopin) (4, 5). These peptides signal through two G proteincoupled receptors, CRF receptors (CRFR)1 and -2, to modulate endocrine, autonomic, and behavioral responses to stress. Although both receptors are found in the central nervous system, CRFR2 is particularly abundant in the periphery, including the heart and systemic vasculature (6-10). UcnII and -III bind selectively to CRFR2, with no appreciable activity at CRFR1 (3, 5).CRF and UcnI both demonstrate vasodilatory, inotropic, and chronotropic effects on the cardiovascular system via activation of CRFR2 on cardiac myocytes and in the systemic vasculature (2,(11)(12)(13)(14). These actions are absent in CRFR2-deficient mice (15, 16). However, both CRF and UcnI also activate CRFR1 in the pituitary and thus stimulate the hypothalamic-pituitaryadrenal axis, complicating the potential use of these peptides for treatment of cardiovascular disorders (14). Therefore, to characterize the...

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Section: Discussionsupporting

confidence: 89%

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Bale

Hoshijima

et al. 2004

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

120

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“…There is clear agreement in the literature that CRF ligands cause mesenteric (Rohde et al, 1996;Barker and Corder, 1999) and coronary (Grunt et al, 1993;Terui et al, 2001;Huang et al, 2002) vasodilatation, but there is no consensus with regard to the mediators involved in those responses or the degree of their dependence on the endothelium. For example, Grunt et al (1993) provided evidence in the isolated rat heart to suggest that the coronary vasodilator action of CRF involved the endothelial release of NO and prostacyclin.…”

Section: Discussionmentioning

confidence: 99%

“…For example, Grunt et al (1993) provided evidence in the isolated rat heart to suggest that the coronary vasodilator action of CRF involved the endothelial release of NO and prostacyclin. In contrast, Terui et al (2001), using the same preparation but with UCN1 rather than CRF as the agonist showed an involvement of prostanoids but not NO.…”

Section: Discussionmentioning

confidence: 99%

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

Gardiner

March²,

Kemp³

et al. 2004

J Pharmacol Exp Ther

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In conscious male Sprague-Dawley rats, we compared regional hemodynamic actions of the selective corticotropin-releasing factor type 2 (CRF 2 ) receptor ligands human and mouse urocortin 2 (hUCN2 and mUCN2, respectively) with those of CRF. Bolus i.v. doses of 3 and 30 pmol kg Ϫ1 hUCN2, mUCN2, or CRF had no significant hemodynamic actions, but at doses of 300 and 3000 pmol kg Ϫ1 , all three peptides caused dosedependent tachycardia and hypotension, with rapid-onset, short-duration, mesenteric vasodilatation and slower-onset, more prolonged hindquarters vasodilatation but little or no change in renal vascular conductance. Pretreatment with the nonselective CRF receptor antagonist astressin or the selective CRF 2 receptor antagonist antisauvagine 30 abolished all the cardiovascular actions of all three peptides. Indomethacin had no effect on responses to hUCN2, and there was no evidence for any involvement of nitric oxide (NO) in the vasodilator actions of hUCN2. There was no evidence that recruitment of angiotensin-and endothelin-mediated vasoconstrictor mechanisms counteracted the vascular actions of hUCN2. The results indicate that the hemodynamic effects of i.v. hUCN2, mUCN2, and CRF depend on activation of CRF 2 receptors and do not involve NO or prostanoids.

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“…3B) vascular system in contrast to its hypertensive effect, which it mediates through the hypothalamic-pituitary-adrenal axis and sympathetic autonomic nervous system (4,(9)(10)(11). Additionally, a direct positive inotropic effect of CRF has been shown on isolated guinea pig ventricular myocardium (28) and on isolated working rat heart (27,34). CRF also induces, in isolated rat heart, a short-term increase in the release of atrial natriuretic factor, perhaps supplying enough to modulate blood pressure through its diuretic, natriuretic, and vasodilatory actions (34).…”

Section: Resultsmentioning

confidence: 99%

“…This receptor is undetectable in other tissues examined, including heart and skeletal muscle (18)(19)(20). However, physiological studies have indicated the presence of a CRF-responsive receptor that mediates a positive inotropic effect in isolated heart (27) and myocardium (28) and suppression of vascular leakage in skeletal muscle (29). Here we report the identification and characterization of another receptor that mediates intracellular responses induced by sauvagine, urotensin I, and CRF.…”

mentioning

confidence: 99%

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

1995

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

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Corticotropin-releasing factor (CRF) mediates many critical aspects of the physiological response to stress. These effects are elicited by binding to specific highaffinity receptors, which are coupled to guanine nucleotide stimulatory factor (Gs)-response pathways. Recently, a gene encoding a receptor for CRF, expressed in pituitary and the central nervous system (PC-CRF receptor), was isolated and characterized. Here we report the identification and characterization of a second, distinct CRF receptor that is expressed primarily in heart and skeletal muscle and exhibits a specific ligand preference and antagonist sensitivity compared with the PC-CRF receptor. We refer to this second receptor as the heart/muscle (HM)-CRF receptor.Corticotropin-releasing factor (CRF) (1) is a member of a family of peptides from different species that act as agonists of the CRF receptor. These peptides include the frog skin peptide, sauvagine (2), and the teleost fish urophysis peptide, urotensin I (3). CRF is a 41-amino acid hypothalamic neuropeptide that plays a central role in coordinating the communications between endocrine, nervous, and immune systems to achieve homeostasis in response to environmental adversities (4, 5). The peptide was originally characterized in the hypothalamo-hypophyseal system but was later found to be widely distributed throughout the central nervous system (CNS), where it appeared to function as a neurotransmitter or neuromodulator (6). In the CNS, CRF initiates the hypothalamic-pituitary-adrenal axis by stimulating the release of adrenocorticotropin (ACTH) and ,B-endorphin from the anterior pituitary. ACTH stimulates adrenal cortex to secrete corticosteroids that, in turn, elicit a wide range of biological responses and exert negative feedback on the hypothalamus and pituitary (4, 5, 7). Both sauvagine and urotensin I have been shown to stimulate the hypothalamic-pituitary-adrenal axis after i.v. administration (8). Intracerebroventricular administration of CRF provokes stress-like responses including activation of the sympathetic nervous system, resulting in an elevation of plasma epinephrine, norepinephrine, and glucose, which results in increased heart rate and mean arterial blood pressure (9, 10). Outside the CNS, CRF immunoreactivity is detectable in multiple peripheral organs, including placenta, adrenal medulla, pancreas, lung, stomach, duodenum, and liver (4, 5). i.v. administration of CRF, sauvagine, and urotensin I has been shown to elicit peripheral systemic responses, including vasodilation (11).CRF functions by binding to a membrane-bound receptor that is coupled to the guanine nucleotide stimulatory factor (G,) signaling protein, resulting in increased intracellular cAMP levels (12,13 (23), and growth hormonereleasing factor ]. The PC-CRF receptor mRNA was found to be most highly expressed in the cerebellum and pituitary and found at lower levels in other brain areas, intestine, and testes. This receptor is undetectable in other tissues examined, including heart and skeletal mus...

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Effects of corticotropin-releasing factor on isolated rat heart activity

Cited by 23 publications

References 0 publications

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

The cardiovascular physiologic actions of urocortin II: Acute effects in murine heart failure

Regional Hemodynamic Actions of Selective Corticotropin-Releasing Factor Type 2 Receptor Ligands in Conscious Rats

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

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