Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats

Malinowska, Barbara; Kwolek, Grzegorz; Göthert, M.

doi:10.1007/s00210-001-0498-6

Cited by 111 publications

(148 citation statements)

References 25 publications

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“…Likewise, anandamide, an endogenous cannabinoid ligand acting on both the VR1 and cannabinoid receptor (CB1), induces similar changes in blood pressure as that of CAP. 17 In the present study, perfusion of CAP at a much lower dose (2.4 nmol) than these previous studies either intravenously or into the left renal pelvis did not alter blood pressure. Whereas CAP at this lower dose given intravenously had no effect on Uflow or UNa, this dose of CAP given into the renal pelvis unilaterally increased bilateral Uflow and UNa, suggesting a pressure-independent and renal pelvis-specific effect of VR1 activation leading to enhancement of renal excretory function.…”

Section: Zhu Et Al Vanilloid Receptor Diuresis Natriuresiscontrasting

confidence: 58%

“…17 It markedly reduces blood pressure with bradycardia presumably evoked by the Bezold-Jarisch reflex (phase I), leading to a brief vasopressor effect (phase II) followed by a prolonged depressor phase (phase III). Likewise, anandamide, an endogenous cannabinoid ligand acting on both the VR1 and cannabinoid receptor (CB1), induces similar changes in blood pressure as that of CAP.…”

Section: Zhu Et Al Vanilloid Receptor Diuresis Natriuresismentioning

confidence: 99%

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Diuresis and Natriuresis Caused by Activation of VR1-Positive Sensory Nerves in Renal Pelvis of Rats

Zhu

Wang

2005

Hypertension

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Abstract-To test the hypothesis that activation of the vanilloid receptor 1 (VR1) expressed in sensory nerves innervating the renal pelvis leads to diuresis and natriuresis, a selective VR1 receptor agonist, capsaicin (2.4 nmol), or vehicle was perfused intravenously or into the left renal pelvis of anesthetized rats at a rate without changing renal perfusion pressure. Mean arterial pressure was not altered by capsaicin administered intravenously or into the renal pelvis. Capsaicin perfusion into the left renal pelvis but not intravenously caused significant increases in urine flow rate and urinary sodium excretion bilaterally in a dose-dependent manner, which were abolished by capsazepine, a selective VR1 receptor antagonist, given ipsilaterally to the renal pelvis or by ipsilateral renal denervation. Capsaicin given intravenously or into the left renal pelvis increased plasma calcitonin gene-related peptide levels to the same extent. Increased plasma calcitonin gene-related peptide levels induced by capsaicin (68.9Ϯ2.8 pg/mL) perfusion into the renal pelvis was prevented either by capsazepine (22.5Ϯ10.1 pg/mL) given ipsilaterally into the renal pelvis or by ipsilateral renal denervation (25.9Ϯ2.3 pg/mL). Taken together, our data show that unilateral activation of VR1-positive sensory nerves innervating the renal pelvis leads to bilateral diuresis and natriuresis via a mechanism that is independent of plasma calcitonin gene-related peptide levels. These data suggest that VR1-positive sensory nerves in the kidney enhance renal excretory function, a mechanism that may be critically involved in sodium and fluid homeostasis. Key Words: natriuresis Ⅲ diuresis Ⅲ sensory nerves Ⅲ vanilloid receptor 1 Ⅲ capsaicin Ⅲ renal pelvis T he renal pelvis is heavily innervated by primary sensory afferent nerves with their nerve terminals distributing in mucous and in proximity to the epithelial cells. 1 The renal pelvis therefore is considered as a sensory organ sensing mechano-stimuli and chemo-stimuli leading to altered renal excretory function such as diuresis and natriuresis. 2,3 Previous studies have shown that ipsilateral obstruction to urine flow or elevation of pressure in the renal pelvis activates renal mechano-sensitive neurons, which results in an increase in ipsilateral afferent renal nerve activity (ARNA). 2,4 Increased ipsilateral ARNA subsequently induces a contralateral diuresis and natriuresis via an inhibition on contralateral efferent renal nerve activity, which is known as the renorenal reflex. 2,4 The vanilloid receptor (VR1), also known as the capsaicin receptor or a member of the transient receptor potential vanilloid subfamily, was cloned by the use of the "hot" pepper-derived vanilloid compound, capsaicin, as a ligand. 5 The VR1 receptor, a ligand gate ion channel, is mainly expressed in a subpopulation of primary sensory afferents and functions to integrate multiple stimuli including proton, heat, and vanilloid compounds such as capsacin. 6 -7 VR1-positive sensory nerves have been implicated to play an...

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Section: Zhu Et Al Vanilloid Receptor Diuresis Natriuresiscontrasting

confidence: 58%

Section: Zhu Et Al Vanilloid Receptor Diuresis Natriuresismentioning

confidence: 99%

Diuresis and Natriuresis Caused by Activation of VR1-Positive Sensory Nerves in Renal Pelvis of Rats

Zhu

Wang

2005

Hypertension

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“…17 Three hours after surgery, baseline MAP and its response to the above-mentioned drugs were determined with the rats fully awake and unrestrained.…”

Section: Methodsmentioning

confidence: 99%

Anandamide-Induced Depressor Effect in Spontaneously Hypertensive Rats

Kaminski

Wang

2003

Hypertension

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Abstract-To test the hypothesis that activation of the vanilloid receptor (VR1) contributes to the anandamide-induced depressor effect in spontaneously hypertensive rats (SHR), we used a selective VR1 antagonist capsazepine (CAPZ) and a selective cannabinoid type 1 receptor antagonist SR141716A in conjunction with a VR1 agonist capsaicin in both SHR and Wistar-Kyoto rats (WKY 4 However, numerous studies indicate that the cardiovascular effect of anandamide is not solely mediated by the CB1 receptor. For example, it has been shown that the vasodilator actions of anandamide in the mesenteric arterial bed are independent of the CB1 receptor. 5 The potent CB1 agonist WIN55212-2 causes vasodilatation in the cat cerebral artery. 6 WIN55212-2 does not cause vasodilatation in the rat mesenteric arterial bed, whereas the endogenous ligand anandamide does cause vasodilatation in this same location. 7 Moreover, in CB1 knockout mice, as well as CB1/CB2 double-knockout mice, anandamide-induced mesenteric vasodilatation is intact. 8 Taken together, these data indicate that receptors distinctive from CB1 and CB2 receptors may mediate the vasodilatation and hypotensive effect of anandamide.One of the potential candidates is the vanilloid receptor 1 (VR1), a ligand-gated ion channel that integrates multiple stimuli, including capsaicin, proton, and heat. 9 -11 This receptor is expressed almost exclusively in primary sensory nerves. It has been demonstrated that VR1 mediates cardiovascular effects of capsaicin, anandamide, and other vanilloid compounds, including vasodilatation in a variety of vascular beds. 12,13 Activation of the VR1 receptor in primary sensory nerves by anandamide induces release of calcitonin generelated peptide (CGRP) from sensory nerve endings and causes vasodilatation. 13 These studies indicate that anandamide-induced activation of the VR1 receptor may play a significant role in blood pressure regulation.In spontaneously hypertensive rats (SHR), the pathogenesis of hypertension appears to be heterogeneous, including the central nervous system, neurohumoral, and renal abnormali-

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“…Capsazepine and ruthenium red, antagonists of the TRPV 1 receptor, dose-dependently inhibit the phase I bradycardic response in anesthetized rats, without affecting the phase III hypotension, which was abolished by the cannabinoid CB 1 receptor antagonist SR141716 (Malinowska et al, 2001) and was also absent in CB 1 receptor knockout mice (Ledent et al, 1999;Járai et al, 1999).…”

Section: Cardiovascular Effects Of Cannabinoids In Vivo Role Of Cb 1mentioning

confidence: 99%

Blood pressure regulation by endocannabinoids and their receptors

2005

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Cannabinoids and their endogenous and synthetic analogs exert powerful hypotensive and cardiodepressor effects by complex mechanisms involving direct and indirect effects on myocardium and vasculature. On the one hand, endocannabinoids and cannabinoid receptors have been implicated in the hypotensive state associated with hemorrhagic, endotoxic and cardiogenic shock, and advanced liver cirrhosis. On the other hand, there is emerging evidence suggesting that the endocannabinergic system plays an important role in the cardiovascular regulation in hypertension. This review is aimed to discuss the in vivo hypotensive and cardiodepressant effects of cannabinoids mediated by cannabinoid and TRPV 1 receptors, and focuses on the novel therapeutical strategies offered by targeting the endocannabinoid system in the treatment of hypertension.

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Anandamide and methanandamide induce both vanilloid VR1- and cannabinoid CB1 receptor-mediated changes in heart rate and blood pressure in anaesthetized rats

Cited by 111 publications

References 25 publications

Diuresis and Natriuresis Caused by Activation of VR1-Positive Sensory Nerves in Renal Pelvis of Rats

Diuresis and Natriuresis Caused by Activation of VR1-Positive Sensory Nerves in Renal Pelvis of Rats

Anandamide-Induced Depressor Effect in Spontaneously Hypertensive Rats

Blood pressure regulation by endocannabinoids and their receptors

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