Signal transduction pathways involved in kinin B₂ receptor‐mediated vasodilation in the rat isolated perfused kidney

Abstract

1 The signal transduction pathways involved in kinin B 2 receptor-related vasodilation were investigated in rat isolated perfused kidneys. During prostaglandin F 2a or KCl-induced constriction, the vasodilator response to a selective B 2 receptor agonist, Tyr(Me) BK by more than 60%, while inhibition of the cannabinoid CB 1 receptor (SR 141716A) had only a moderate eect. 5 Acetylcholine induced a concentration-dependent relaxation with characteristics nearly similar to the response to Tyr(Me) 8 BK. In contrast, the relaxation elicited by sodium nitroprusside was potentiated in the absence of NO (L-NOARG or removal of endothelium) but remained unchanged otherwise. 6 These results indicate that the activation of kinin B 2 receptors in the rat isolated kidney elicits an endothelium-dependent vasorelaxation, mainly dependent on the activation of charybdotoxinsensitive Ca 2+ -activated K + channels. In addition, cytochrome P450 derivatives appear to be involved.

EDHF-mediated vasodilation involves different mechanisms in normotensive and hypertensive rat lungs

“…In contrast to the blunting of acute hypoxic pulmonary vasoconstriction by endogenously generated PGI 2 and NO in isolated rat lungs (28,37,39,41), our results suggested no role for tonic EDHF activity in moderating hypoxic vasoconstriction in either normotensive or hypertensive rat lungs. This contradicts the speculation of Hasunuma et al (28), based on effects of the nonselective K ϩ channel blocker tetraethylammonium, that EDHF moderates hypoxic vasoconstriction in normal rat lungs.…”

“…Thus the objectives of this study were to investigate whether EDHF activity contributed to the regulation of either basal or hypoxic pulmonary vascular tone and to examine the mechanism of EDHF-mediated pulmonary vasodilation in isolated normotensive and hypoxia-induced hypertensive rat lungs. After inhibition of both PGI 2 and NO synthesis, we tested the effects of inhibitors of EDHF (charybdotoxin plus apamin), CYP450 (7-ethoxyresorufin and sulfaphenazole), and gap junctions (18␣-glycyrrhetinic acid and palmitoleic acid) on basal perfusion pressure and acute hypoxic vasoconstriction and on the vasodilation induced by thapsigargin during hypoxic vasoconstriction.…”

Control of ENaC-Mediated Sodium Reabsorption in the Distal Nephron by Bradykinin

“…Moreover, putative PI(4,5)P 2 binding sites in the intracellular N-termini of β-and γ-ENaC subunits have been recently reported (Kunzelmann et al, 2005;Pochynyuk et al, 2007). In addition, activation of BK signaling is known to stimulate NO production via eNOS-dependent pathways in cortex kidney slices (Adler et al, 2001), augment production of cytochrome P450 derivatives in perfused rat kidney (Bagate et al, 2001), and activate PKC-PLA 2 (Lal, Kennedy, Proulx, & Hebert, 1997) and PLD-ceramide/phosphatidic acid (Liu, Kleine, Nasrallah, & Hebert, 1999) signaling cascades in rabbit CCD cells. All these pathways can also exert inhibitory actions on ENaC (Bao et al, 2007;Guo, Alli, Eaton, & Bao, 2013;Pavlov et al, 2011).…”

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

“…Bradykinin induces relaxation of vascular smooth muscle via stimulation of B2 receptors, which in turn stimulates constitutively expressed endothelial nitric oxide (NO) synthase (eNOS) to produce NO, induces cyclooxygenase-dependent production of prostacyclin and other prostanoids, as well as superoxide, activates charybdotoxin-sensitive K+ channels, and induces the formation of epoxyeicosatrienoic acids by cytochrome P-450 epoxygenase [122][123][124]. In addition to its actions on arterial and arteriolar vascular smooth muscle, bradykinin also exerts powerful pro-inflammatory effects in postcapillary venules.…”