Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes

Laugwitz, Karl‐Ludwig; Ungerer, Martin; Schöneberg, Torsten; Weig, Hans-Jörg; Kronsbein, Kai; Moretti, Alessandra; Hoffmann, Katrin; Seyfarth, Melchior; Schultz, Günter; Schömig, Albert

doi:10.1161/01.cir.99.7.925

Cited by 26 publications

(18 citation statements)

References 25 publications

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“…The clinical serum level of vasopressin of the healthy human ranges from 0.4 to 4 pmol/L, 3 but there was a large discrepancy between the clinical vasopressin concentration and that which inhibited the KATP channel in the cellattached mode of the present study. We explain this difference as follows.…”

Section: Clinical Implications Of Vasopressincontrasting

confidence: 64%

“…Two types of vasopressin receptors are known to couple to various signal transduction pathways. 3,7,[12][13][14][15] We examined which type of receptor is involved in the vasopressin-induced inhibition on KATP channels using desGly 9 -[ -Mercapto-, -cyclopentamethylene-propionyl 1 , O-Et-Tyr 2 -Val 4 -Arg 8 ]-vasopressin (1 mol/L), which has potent V1 receptor antagonism and weak V2 receptor antagonism, manning compound (1 mol/L), a V1 receptor-selective antagonist, and OPC-31260, a V2 receptor-selective antagonist. 20 These compounds used alone did not change the channel activity induced by metabolic stress.…”

Section: Vasopressin Acts On Katp Channels Through the V1 Receptormentioning

confidence: 99%

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Vasopressin Inhibits Sarcolemmal ATP-Sensitive K+ Channels via V1 Receptors Activation in the Guinea Pig Heart.

Tsuchiya

Maruyama

et al. 2002

Circ J

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asopressin is one of the physiologically active peptides that regulate humoral immunity by promoting reabsorption of water in the kidney and simultaneously having a potent vasoconstrictive action on vascular smooth muscle by increasing the production of inositol 1,4,5-triphosphate (IP3) and 1,2-diacylglycerol (DG) and activating the voltage-dependent Ca channel, which results in elevation of the intracellular Ca concentration. 1,2 Recently, it has been reported that secretion of vasopressin increases in pathophysiological conditions such as angina pectoris, acute myocardial infarction and chronic heart failure. 3 During such conditions of metabolic inhibition, activation of the sarcolemmal KATP channel 4 is known to regulate Ca 2+ entry and myocardial contractility in order to lessen the myocardial damage. 5,6 Moreover, activation of this channel minimizes the infarct area in animal models 7 and elicits a cardioprotective action in dogs with pacinginduced heart failure. 8 On the other hand, its activation has been reported to shorten the action potential duration, thereby in part acting arrhythmogenically in acute ischemia. 9,10 Moreover, Martin et al 2 reported that vasopressin inhibited the sarcolemmal KATP channels and activated the voltage-dependent Ca channel, thereby regulating insulin secretion in rat pancreatic -cells. Wakatsuki et al 11 reported that vasopressin activated Ca-activated K channels and simultaneously controlled vascular tone by suppressing sarcolemmal KATP channels in porcine coronary vascular smooth muscle cells in the cell-attached configuration. More recently, it has been reported that the vasopressin V1 Circulation Journal Vol.66, March 2002receptor couples to protein kinase C via activation of phospholipase C and that vasopressin V2 receptor links to G protein coupled protein kinase including adenylate cyclase. [12][13][14][15] In the central nervous system, Easaw 16 showed that vasopressin-inhibited the voltage-dependent outward current via the V1 receptor, and it activated the same current via the V2 receptor.Therefore vasopressin regulates excitation of neurons in a diagonal band of the rat. However, the action of vasopressin in the heart still remains controversial. The present study aimed to examine the physiological implication of vasopressin's effects on sarcolemmal KATP channel in enzymatically isolated guinea pig ventricular myocytes using both cell-attached and inside-out configurations. Methods Preparation of Single Ventricular CardiomyocytesAdult male guinea pigs of 250-300 g were anesthetized with pentobarbital sodium (40-50 mg/kg ip) and isolated ventricular cells were obtained using the collagenase perfusion method. 17 In brief, the chest was briefly opened under artificial ventilation, the aorta cannulated and the heart quickly dissected. Using a Langendorff apparatus, the heart was retrogradedly perfused with normal Tyrode's solution for about 5 min to wash out the blood in the vessels, followed by nominally Ca 2+ -free Tyrode's solution for about 3 min at 36°C. The h...

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Section: Clinical Implications Of Vasopressincontrasting

confidence: 64%

Section: Vasopressin Acts On Katp Channels Through the V1 Receptormentioning

confidence: 99%

Vasopressin Inhibits Sarcolemmal ATP-Sensitive K+ Channels via V1 Receptors Activation in the Guinea Pig Heart.

Tsuchiya

Maruyama

et al. 2002

Circ J

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“…The V1 receptor is coupled to phospholipase C (PLC)-␤ while V2 is coupled to G s and adenylyl cyclase. Viral-mediated gene transfer of V2 in adult rat ventricular myocytes resulted in dose-dependent expression, an increase in cAMP formation, and an increased amplitude of contraction in isolated myocytes that was blocked by a V2-specific vasopressin antagonist (473). Coronary-based adenoviral gene delivery to the myocardium also improved fractional shortening and the rate of contraction in response to V2 stimulation (953).…”

Section: Downstream ␤-Ar Signalingmentioning

confidence: 96%

Designing Heart Performance by Gene Transfer

Davis¹,

Westfall²,

Townsend³

et al. 2008

Physiological Reviews

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The birth of molecular cardiology can be traced to the development and implementation of high-fidelity genetic approaches for manipulating the heart. Recombinant viral vector-based technology offers a highly effective approach to genetically engineer cardiac muscle in vitro and in vivo. This review highlights discoveries made in cardiac muscle physiology through the use of targeted viral-mediated genetic modification. Here the history of cardiac gene transfer technology and the strengths and limitations of viral and nonviral vectors for gene delivery are reviewed. A comprehensive account is given of the application of gene transfer technology for studying key cardiac muscle targets including Ca2+handling, the sarcomere, the cytoskeleton, and signaling molecules and their posttranslational modifications. The primary objective of this review is to provide a thorough analysis of gene transfer studies for understanding cardiac physiology in health and disease. By comparing results obtained from gene transfer with those obtained from transgenesis and biophysical and biochemical methodologies, this review provides a global view of cardiac structure-function with an eye towards future areas of research. The data presented here serve as a basis for discovery of new therapeutic targets for remediation of acquired and inherited cardiac diseases.

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“…Single myocytes were isolated from the left ventricle of control and 15 days paced failing rabbits, and cultured in modified M199 medium on laminin-precoated glass slides, as described (9). Two hours after plating, cells were subjected to detection of activated caspase-3.…”

Section: Construction and Purification Of Recombinant Adenovirusmentioning

confidence: 99%

Essential myosin light chain as a target for caspase-3 in failing myocardium

Moretti

Weig

Ott

et al. 2002

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

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Programmed cell death involves the activation of caspase proteases that can mediate the cleavage of vital cytoskeletal proteins. We have recently reported that, in failing cardiac myocytes, caspase-3 activation is associated with a reduction in contractile performance. In this study we used a modified yeast two-hybrid system to screen for caspase-3 interacting proteins of the cardiac cytoskeleton. We identified ventricular essential myosin light chain (vMLC1) as a target for caspase-3. By sequencing and site-directed mutagenesis, a noncanonical cleavage site for caspase-3 was mapped to the C-terminal DFVE 135 G motif. We demonstrated that vMLC1 cleavage in failing myocardium in vivo is associated with a morphological disruption of the organized vMLC1 staining of sarcomeres, and with a reduction in myocyte contractile performance. Adenoviral gene transfer of the caspase inhibitor p35 in vivo prevented caspase-3 activation and vMLC1 cleavage, with positive impact on contractility. These data suggest that direct cleavage of vMLC1 by activated caspase-3 may contribute to depression of myocyte function by altering cross-bridge interaction between myosin and actin molecules. Therefore, activation of apoptotic pathways in the heart may lead to contractile dysfunction before cell death.

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Adenoviral Gene Transfer of the Human V2 Vasopressin Receptor Improves Contractile Force of Rat Cardiomyocytes

Cited by 26 publications

References 25 publications

Vasopressin Inhibits Sarcolemmal ATP-Sensitive K+ Channels via V1 Receptors Activation in the Guinea Pig Heart.

Vasopressin Inhibits Sarcolemmal ATP-Sensitive K+ Channels via V1 Receptors Activation in the Guinea Pig Heart.

Designing Heart Performance by Gene Transfer

Essential myosin light chain as a target for caspase-3 in failing myocardium

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