RELEASE OF <sup>3</sup>H‐PURINES FROM [<sup>3</sup>H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE

Fredholm, Bertil B.; Hedqvist, Per

doi:10.1111/j.1476-5381.1978.tb17295.x

Cited by 69 publications

(16 citation statements)

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“…tion, which was blocked by A 1 -receptor inhibition (28). ANG II may elevate interstitial/tissue levels of adenosine in the kidney via increased release or reduced metabolism of adenosine (15,19). Franco et al (15) demonstrated twofold higher adenosine levels with ANG II and that enhanced renal vasoconstriction in ANG II-treated rats was reverted by A 1 -receptor inhibition.…”

Section: Discussionmentioning

confidence: 99%

“…Studies in isolated and perfused afferent arterioles have shown that interaction between adenosine and ANG II potentiates the contractile response (28). Moreover, ANG II has been shown to elevate intrarenal adenosine concentrations, either by increased release (19) or decreased metabolism of adenosine (15). As yet the role of adenosine A 1 -receptors in development of hypertension is not clear.…”

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confidence: 97%

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Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

Gao

Patzak

Sendeski

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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Increased preglomerular reactivity, due to reduced nitric oxide (NO) production or increased levels of ANG II and reactive oxygen species (ROS), has been linked to hypertension. Using A1-receptor knockout (A1 Ϫ/Ϫ ) and wild-type (A1 ϩ/ϩ ) mice we investigated the hypothesis that A1-receptors modulate arteriolar and blood pressure responses during NO synthase (NOS) inhibition or ANG II treatment. Blood pressure and renal afferent arteriolar responses were measured in nontreated mice and in mice with prolonged N -nitro-L-arginine methyl ester hydrochloride (L-NAME) or ANG II treatment. The hypertensive responses to L-NAME and ANG II were clearly attenuated in A1 Ϫ/Ϫ mice. Arteriolar contractions to L-NAME (10 Ϫ4 mol/l; 15 min) and cumulative ANG II application (10 Ϫ12 to 10 Ϫ6 mol/l) were lower in A1 Ϫ/Ϫ mice. Simultaneous treatment with tempol (10 Ϫ4 mol/l; 15 min) attenuated arteriolar responses in A1 ϩ/ϩ but not in A1 Ϫ/Ϫ mice, suggesting differences in ROS formation. Chronic treatment with L-NAME or ANG II did not alter arteriolar responses in A1 Ϫ/Ϫ mice, but enhanced maximal contractions in A1 ϩ/ϩ mice. In addition, chronic treatments were associated with higher plasma levels of dimethylarginines (asymmetrical and symmetrical) and oxidative stress marker malondialdehyde in A1 ϩ/ϩ mice, and gene expression analysis showed reduced upregulation of NOS-isoforms and greater upregulation of NADPH oxidases. In conclusion, adenosine A1-receptors enhance preglomerular responses during NO inhibition and ANG II treatment. Interruption of A1-receptor signaling blunts L-NAME and ANG II-induced hypertension and oxidative stress and is linked to reduced responsiveness of afferent arterioles. preglomerular function; hypertension; oxidative stress; tubuloglomerular feedback; reactive oxygen species THE RENAL AFFERENT ARTERIOLE is the effector site of the tubuloglomerular feedback (TGF) mechanism that regulates glomerular perfusion and filtration (43). In this way, TGF contributes to the renal autoregulation and the long-term blood pressure control. Osswald et al. (37) first proposed that TGFinduced afferent arteriolar vasoconstriction may be elicited through local generation of adenosine following increased NaCl transport. Adenosine, via activation of A 1 -receptors, has been demonstrated to mediate TGF responses in both rats (16, 44) and mice (3, 46), whereas activation of A 2 -receptors (A 2A or A 2B ) and nitric oxide (NO) release may attenuate the response (11). Elevated levels of ANG II and reactive oxygen species (ROS) may enhance TGF response and preglomerular reactivity (49, 56) and have been associated with hypertension in several experimental models (5,6,34,48,56,57). There is considerable evidence for a synergistic interaction between ANG II and adenosine in the kidney (17), and this importantly contributes to regulation of the renal microcirculation (28). Although an interaction between ANG II and adenosine was described more than three decades ago (45), the mechanisms of synergism and its role in blood pressure ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

Gao

Patzak

Sendeski

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In the present experiments release of purines could be induced not only by nerve stimulation but also by noradrenaline, further supporting the non-neuronal origin of the purines. In the kidney (Fredholm & Hedqvist, 1978), heart (Fredholm, Hedqvist, Vernet & Wennmalm, 1979), nictitating membrane (Luchelli-Fortis, Fredholm & Langer, 1979) and vas deferens (Fredholm, Fried & Hedqvist, 1980) the bulk of purines released following nerve stimulation seem to derive from non-neuronal elements. It is, however, not possible to generalize since there are several reports suggesting that release of purines may also occur from nerves.…”

Section: Discussionmentioning

confidence: 99%

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

Fredholm¹,

Sollevi²

1981

The Journal of Physiology

154

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SUMMARY1. Plasma and adipose tissue purine nucleosides were assayed by reversed phase high-performance liquid chromatography after purification of the samples on phenylboronate affinity gel.2. The adenosine content of unstimulated subcutaneous adipose tissue was close to 1 n-mole/g. The concentrations of adenosine and inosine in canine arterial plasma were 0-26+0-03 and 0 16±+003gM, respectively. In venous plasma from the canine subcutaneous adipose tissue the corresponding values were 0-32 + 0 04 and 0-28 ± 0-06 /LM under basal conditions. The arterio-venous concentration difference of adenosine was linearly dependent upon the arterial adenosine concentration. At arterial concentrations below 0'3 ,lM there was a net production of adenosine; above 0 3 /SM there was a net extraction of approximately 77 % of the adenosine.Adenosine was extensively eliminated in blood. The major part of this elimination could be accounted for by metabolism to inosine, hypoxanthine and uric acid.3. Following sympathetic nerve stimulation (4 Hz for 20 min) the rate of adenosine outflow from adipose tissue increased from 0-33 + 0-22 to a peak value of 1'2 + 0-26 n-mole/min. This corresponds to a net release of 8-7 + 3 0 n-mole/100 g tissue. Inosine outflow rose from 064 + 037 to 5-3 + 1-4 n-mole/min, corresponding to a net release of 24-6+8-7 n-mole/100 g. Nerve stimulation also increased the release of [3H]purines from [3H]adenine pre-labelled adipose tissue. The fractional release increased 15-fold after stimulation. The radioactivity was mainly in the form of hypoxanthine, inosine and uric acid while adenosine was a minor component. When metabolism in blood was inhibited by dipyridamole and an adenosine deaminase inhibitor nerve-stimulation-induced release of [3H]purines was mainly in the form of adenosine.4. Noradrenaline injection also induced a release of radioactive purines and of inosine. On the other hand, the outflow of endogenous adenosine was very small.5. The present results demonstrate that under basal conditions adenosine is present in arterial and venous canine plasma. The free extracellular tissue level may be similar to the basal arterial adenosine concentration. Sympathetic nerve stimulation and noradrenaline induces a marked release of adenosine which is rapidly metabolized in the tissue and blood stream to inosine, hypoxanthine and uric acid. In adipose tissue the levels of adenosine reached after adrenergic stimulation appear high enough to be of physiological relevance.

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“…Similar evidence suggesting the release of ATP from postsynaptic sites as well as neuro nal ones was presented in the rabbit kidney (17), the rat caudal artery (18) and rat vas def erens (4). However, it is not always easy to ascertain whether the source of ATP is nerves or muscles.…”

Section: Effects Of Nka On 3h and 14c Efflux Evoked By Electrical Stimentioning

confidence: 68%

Postsynaptic Potentiation of Neurotransmission by Neurokinin A in Rat Vas Deferens.

1992

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-Effects of neurokinin A (NKA) on sympathetic neurotransmission were studied in rat vas deferens. Although neither prazosin, an a 1-adrenoceptor blocker, nor a,,8-methylene adenosine triphosphate, a P2-purinoceptor blocker, inhibited the NKA-induced contractions in the epididymal site, high concentration of NKA-induced contractions in the prostatic site were slightly decreased by either of the two blockers. Treatment with guanethidine, which prevents the release of sympathetic transmitters from presynaptic nerve endings, also had no effect on NKA-induced contractions in either site. To investigate the effects of NKA on the adrenergic and purinergic neurotransmission in more detail, we measured transmitter release by using [3H]norepinephrine or [14C]adenosine. Neither spontaneous or nor evoked 3H efflux, indicating NE release, was affected by NKA in either site. NKA enhanced 14C efflux, indicating ATP release, evoked by electrical stimulation in the epididymal site, which may be originated from smooth muscle. In the prostatic site, contractions induced by electrical stimulation were enhanced in spite of no increase in 3H or 14C efflux. These results suggest that: 1) NKA has no effect on presynaptic nerve terminals in both sites, 2) NKA potentiates the effects of neurotransmitters in the prostatic site, and 3) NKA modulates the neurotransmission.Neurokinin A (NKA), which is structurally related to substance P, exerts a great variety of effects on various tissues (1-3). Rat vas deferens is a good model for investigating sympathetic neurotransmission, and its adren ergic and purinergic properties have been ex tensively characterized.It is well-known that the smooth muscle of the rat vas deferens receives a dense plexus of adrenergic fibers, and stimulation of the hypo gastric nerve mainly results in an overflow of endogenous NE from the tissue. Much evi dence has also shown that ATP is released by nerve stimulation (4 8) and induces contrac tion (9-11) in several sympathetically inner vated tissues, including rat vas deferens. The presence of NK2 receptors both in the auto nomic nerves and in the smooth muscle of rat vas deferens has been reported, and potentia tion of electrical stimulation-evoked twitches by NKA in the prostatic site was regarded as a result of facilitating release of transmitters (12). However, under this condition, both pre synaptic and postsynaptic effects can equally contribute to the potentiation. In the previous report (13), we have characterized NKA-in duced contractions of rat vas deferens and dem onstrated that there are region-dependent

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RELEASE OF ³H‐PURINES FROM [³H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE

Cited by 69 publications

References 20 publications

Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

Postsynaptic Potentiation of Neurotransmission by Neurokinin A in Rat Vas Deferens.

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RELEASE OF 3H‐PURINES FROM [3H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE

Cited by 69 publications

References 20 publications

Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

Adenosine A1-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

The release of adenosine and inosine from canine subcutaneous adipose tissue by nerve stimulation and noradrenaline.

Postsynaptic Potentiation of Neurotransmission by Neurokinin A in Rat Vas Deferens.

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Product

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RELEASE OF ³H‐PURINES FROM [³H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE

Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment

Adenosine A₁-receptor deficiency diminishes afferent arteriolar and blood pressure responses during nitric oxide inhibition and angiotensin II treatment