Acetylcholine-induced vasodilation in the perfused kidney of the streptozotocin-induced diabetic rat: role of prostacyclin

Kamata, Katsuo; Hosokawa, Masao; Matsumoto, Takayuki; Kobayashi, Tsuneo

doi:10.1540/jsmr.42.159

Cited by 18 publications

(9 citation statements)

References 59 publications

(67 reference statements)

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“…Previously, it has been demonstrated that in established STZ diabetic rats, blockade of cyclooxygenase activity was essentially without effect on RBF (4). However, under some conditions in the presence of reduced NO bioavailability, there may be a compensatory increase in the contribution of vasodilator prostaglandins (16). In contrast to our present findings in the kidney, we have previously found that diabetes-induced attenuation of the hyperemic response to ACh in the hindlimb and mesenteric circulations in vivo is chiefly attributable to diminished EDHF function (26).…”

Section: Discussioncontrasting

confidence: 99%

In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes

Edgley

Tare²,

Evans³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Edgley AJ, Tare M, Evans RG, Skordilis C, Parkington HC. In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes. Am J Physiol Regul Integr Comp Physiol 295: R829 -R839, 2008. First published July 16, 2008 doi:10.1152/ajpregu.00861.2007.-We assessed the relative contributions of endothelium-derived relaxing factors to renal vasodilation in vivo and determined whether these are altered in established streptozotocin-induced diabetes. In nondiabetic rats, stimulation of the endothelium by locally administered ACh or bradykinin-induced transient renal hyperemia. Neither basal renal blood flow (RBF) nor renal hyperemic responses to ACh or bradykinin were altered by blockade of prostanoid production (indomethacin) or by administration of charybdotoxin (ChTx) plus apamin to block endothelium-derived hyperpolarizing factor (EDHF). In contrast, combined blockade of nitric oxide (NO) synthase, N -nitro-L-arginine methyl ester (L-NAME), and prostanoid production reduced basal RBF and the duration of the hyperemic responses to ACh and bradykinin and revealed a delayed ischemic response to ACh. Accordingly, L-NAME and indomethacin markedly reduced integrated (area under the curve) hyperemic responses to ACh and bradykinin. Peak increases in RBF in response to ACh and bradykinin were not reduced by L-NAME and indomethacin but were reduced by subsequent blockade of EDHF. L-NAME plus indomethacin and ChTx plus apamin altered RBF responses to endothelium stimulation in a qualitatively similar fashion in diabetic and nondiabetic rats. The integrated renal hyperemic responses to ACh and bradykinin were blunted in diabetes, due to a diminished contribution of the component abolished by L-NAME plus indomethacin. We conclude that NO dominates integrated hyperemic responses to ACh and bradykinin in the rat kidney in vivo. After prior inhibition of NO synthase, EDHF mediates transient renal vasodilation in vivo. Renal endotheliumdependent vasodilation is diminished in diabetes due to impaired NO function. kidney circulation; acetylcholine; bradykinin; endothelium-derived hyperpolarizing factor; nitric oxide THE VASCULAR ENDOTHELIUM MEDIATES relaxation of the underlying smooth muscle via the actions of several vasodilators, including nitric oxide (NO), prostanoids (e.g., prostacyclin), and an endothelium-derived hyperpolarizing factor (EDHF) (36). The relative importance of these vasodilators varies across different vascular beds (32). While NO is critical in the larger vessels, EDHF assumes greater importance in smallresistance arteries (34).Endothelium-derived NO, prostanoids, and EDHF have all been implicated in the control of renal vascular tone in vitro. Inhibition of NO synthase (NOS) significantly reduces endothelium-dependent vasodilation in the renal bed, with an additional role of prostanoid revealed by inhibition of cyclooxygenase (COX) (30). Following inhibition of NOS and COX, there remains a vasodilator response to endothelial stimulation by A...

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Section: Discussioncontrasting

confidence: 99%

In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes

Edgley

Tare²,

Evans³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Moreover, several reports have suggested that enhanced production of vasodilator PGs by the glomeruli may be only associated with an increased GFR in STZ-induced diabetes, but also implicated in the progression of diabetic nephropathy (Cheng et al, 2002;Cheng and Harris, 2004;Natarajan and Nadler, 2004). Furthermore, in a previous report, we noted an AChinduced increment in 6-keto-prostaglandin F1α (a metabolite of prostacyclin) in the perfusate issuing from the STZ-induced diabetic kidney (Kamata and Hosokawa, 1997b).…”

Section: Discussionmentioning

confidence: 47%

“…This speculation is in line with the previous findings (a) that COX can convert 20-HETE into the renal vasodilator 20-OH-PGE2 and constrictor 20-OH-PGH2 (McGiff and Quilley, 1999) and (b) that 5,6-EET, a renal vasodilator metabolite produced from AA via the action of CYP450, requires COX for the expression of its vasoactivity (since the response is inhibited by indomethacin and other aspirin-like drugs) (Carroll et al, 1993). We found previously that in the perfused kidney, AA (10 -5 M) did not, by itself, induces vasoconstriction (Kamata and Hosokawa, 1997b), but did transiently increase the perfusion pressure in the methoxamine-preconstricted preparation. AA is known to be a Ca 2+ -sensitizing agent (Somlyo and Somlyo, 1994;Hirano et al, 2004).…”

Section: Discussionmentioning

confidence: 73%

“…Moreover, Pfister et al (1996) reported that the ability of AA, but not of ACh, to induce relaxation depends on a non-COX metabolite from endothelial cells that relaxes rabbit vascular smooth muscle. In our previous studies, we found that ACh-induced endothelium-dependent relaxation was impaired in the perfused kidney of the streptozotocin (STZ)-induced diabetic rat (Kamata and Hosokawa, 1997b;Kamata and Hayashi, 1999;Kamata and Yamashita, 1999), and we provided evidence that this endothelial dysfunction may be due to decreased nitric oxide (NO) or EDHF signaling (Kamata and Hosokawa, 1997b). Moreover, we found that ACh increased the level of 6-keto-prostaglandin F1α (a metabolite of prostacyclin) in the effluent collected from the perfused kidney of the STZ-induced diabetic rat, and we suggested that an elevated level of prostacyclin may contribute to the alteration of renal vascular tone in diabetic states (Kamata and Hosokawa, 1997b).…”

Section: Introductionmentioning

confidence: 98%

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Altered arachidonic acid-mediated responses in the perfused kidney of the streptozotocin-induced diabetic rat

Kamata

Hosokawa

Matsumoto

et al. 2006

J. Smooth Muscle Res.

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Using perfused kidneys isolated from age-matched controls and streptozotocin (STZ)-induced diabetic rats, we investigated the effects of arachidonic acid (AA) on perfusion pressure in the presence of methoxamine. AA elicited a transient contraction followed by a sustained relaxation in each group. The amplitude of contraction was smaller in the diabetic group than in the control group, whereas the amplitude of the sustained relaxation was greater in the former than in the latter group. In the diabetic group, the AA-induced sustained relaxation was completely inhibited by indomethacin [cyclooxygenase (COX) inhibitor], SKF525A [cytochrome P450 (CYP450) inhibitor], or clotrimazole (epoxygenase inhibitor), but not by furegrelate [thromboxane A2 (TXA2)-synthase inhibitor], SQ29548 (TXA2-receptor antagonist), or baicalein [lipoxygenase (LOX) inhibitor]. In the diabetic kidney, more-or-less additive inhibitions of the AAinduced relaxation were seen when indomethacin was given with either SKF525A or clotrimazole. These results suggest that in the STZ-induced diabetic perfused kidney, vasorelaxant metabolites derived from AA (probably COX and/or CYP450 metabolites) are increased, and may serve to regulate vascular tone.

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“…The functional changes are acutely reversed by systemic administration of insulin [11,12]. Evidence suggests that the underlying defect may be due to a reduction in nitric oxide synthesis or, in some instances, an increase in the synthesis of constrictor factors [14].…”

Section: Introductionmentioning

confidence: 99%

Influence of insulin on the microvascular response to inflammatory mediators in neonatal streptozotocin diabetic rats

Rastelli

Akamine²,

Oliveira³

et al. 2005

Inflamm. res.

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Acetylcholine-induced vasodilation in the perfused kidney of the streptozotocin-induced diabetic rat: role of prostacyclin

Cited by 18 publications

References 59 publications

In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes

In vivo regulation of endothelium-dependent vasodilation in the rat renal circulation and the effect of streptozotocin-induced diabetes

Altered arachidonic acid-mediated responses in the perfused kidney of the streptozotocin-induced diabetic rat

Influence of insulin on the microvascular response to inflammatory mediators in neonatal streptozotocin diabetic rats

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