Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two subclasses of adenosine receptors, A1 and A2, have been described. The purpose of these experiments was to determine and compare the renal effects of several adenosine receptor agonists: adenosine (Ado), 2-chloroadenosine (2CA, nonselective), N6-cyclohexyladenosine (CHA, A1 selective), and N6-ethylcarboxamide adenosine (NECA, A2 selective). Rat kidneys were perfused at constant pressure (105 +/- 5 mmHg) using a Krebs-Henseleit buffer containing 3.5 g/100 ml Ficoll and 1.0 g/100 ml bovine serum albumin. Three clearance periods were obtained in each kidney, i.e., control, experimental [drug at 1 microM or vehicle (NaCl)], and recovery. Perfusate flow was increased by Ado, 2CA, and NECA but not affected by CHA. Glomerular filtration was increased by NECA, decreased by CHA, and not affected by Ado and 2CA. Afferent arteriolar resistance was decreased by NECA, increased by CHA, and unaffected by Ado and 2CA. Efferent arteriolar resistance was decreased by all agonists. CHA tended to decrease renin secretion whereas NECA significantly increased it. The results suggest that the renal vasculature possesses both A1 and A2 adenosine receptors and that activation of A2 receptors mediates arteriolar dilation and stimulation of renin secretion whereas activation of A1 receptors mediates arteriolar constriction and possibly inhibition of renin secretion.
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PMID:Effects of adenosine receptor agonists in the isolated, perfused rat kidney. 608 92

In the present experiments, we tested the hypothesis that renal denervation would attenuate or abolish some of the renal effects of cyclohexyladenosine, a nonmetabolized adenosine receptor agonist. A paired design (left kidney sham-denervated or denervated versus the innervated right kidney) was used in anesthetized rats. Intravenous cyclohexyladenosine (2.3 nmol/min) reduced para-aminohippurate and inulin clearances in both denervated and sham-denervated kidneys; these effects were increased rather than decreased in denervated kidneys. Similarly, cyclohexyladenosine decreased the excretion of Na+ and K+ more in denervated than in innervated kidneys. Renal plasma flow was decreased by cyclohexyladenosine, without a corresponding increase in the arteriorenal venous difference in plasma renin concentrations, and arterial plasma renin concentration decreased in all rats given cyclohexyladenosine, suggesting inhibition of renin secretion. No differences in the latter variables were noted in denervated versus sham-denervated kidneys. Since cyclohexyladenosine produced effects in denervated kidneys which were equal to or greater than the effects in sham-denervated kidneys, it is concluded that these effects are mediated by direct actions, rather than by inhibition of transmitter release from the renal nerves.
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PMID:Effects of renal denervation on the renal responses of anesthetized rats to cyclohexyladenosine. 638 28

Adenosine is a major inhibitory neuromodulator in the central nervous system. One of the receptors mediating the central effects of adenosine is the adenosine A1 receptor. We performed a systematic mutation scan of the coding region of the adenosine A1 receptor gene to explore its variability in the general population. Investigating 40 unrelated healthy subjects by single-strand conformation analysis no sequence changes of likely functional relevance were observed. We detected, however, a frequent T to G substitution at nucleotide position 716 which constitutes the first variant described in an adenosine receptor gene. It was used for fine scale linkage mapping of the A1 gene. Employing a polymerase-chain-reaction-based restriction assay, we genotyped 7 CEPH families (Centre d'Etude du Polymorphisme Humaine) and mapped the receptor in a gene cluster around the renin gene on chromosome 1q31-32.1. In addition, we utilized the 716T/G polymorphism to demonstrate biallelic expression of the adenosine A1 receptor gene in adult human brain.
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PMID:Human adenosine A1 receptor gene: systematic screening for DNA sequence variation and linkage mapping on chromosome 1q31-32.1 using a silent polymorphism in the coding region. 767 73

The mechanism by which aging decreases the cardiac chronotropic response in human subjects is unknown. We investigated the role of endogenous adenosine in attenuating the chronotropic response to beta-adrenoceptor stimulation due to aging by employing the adenosine receptor antagonist, theophylline. Sixteen healthy elderly (67.1 +/- 1.3 yrs) and sixteen healthy young (26.1 +/- 0.6 yrs) subjects were studied. The bolus dose of isoproterenol necessary to increase the heart rate 25 beats per minute (I25) was determined by calculating the log dose response curve before and after a 30-min infusion of theophylline (6.5 mg/kg) in each subject. In addition, the effect of theophylline on the orthostatic increase in plasma renin activity (PRA) was determined. The I25 for the elderly and young groups were 34.55 +/- 6.98 and 10.85 +/- 1.93 ng/kg, respectively (p < .01). After theophylline administration, the difference in I25 in the two groups was no longer present (13.32 +/- 2.72 vs 7.46 +/- 1.26 ng/kg). The dose ratios (I25 after theophylline/I25 before theophylline) in the elderly and young groups were 0.43 +/- 0.06 and 0.82 +/- 0.14, respectively (p < .05). After the administration of theophylline, the orthostatic increase in PRA was enhanced more in the elderly subjects (0.53 +/- 0.23 vs 1.54 +/- 0.35 ng AI/ml/hr; p < .01) than in the young (1.31 +/- 0.23 vs 2.49 +/- 0.53 ng AI/ml/hr; p-value n.s.). Plasma norepinephrine changes after theophylline and postural norepinephrine changes after theophylline were not different in the two age groups. Excessive adenosine production or effect is partly responsible for the cardiac chronotropic resistance to isoproterenol and the diminished postural change in PRA in the elderly.
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PMID:The role of adenosine in promoting cardiac beta-adrenergic subsensitivity in aging humans. 774 91

The purpose of this study was to examine (1) whether endogenous adenosine receptors inhibit the release of epinephrine and norepinephrine from adrenal medulla in response to physiological and pharmacological stimuli and (2) whether the renin-angiotensin system modulates this effect of endogenous adenosine. We used a conscious animal model to approximate normal physiological conditions. Male Sprague-Dawley rats were treated with a surface adenosine receptor antagonist, 1,3-dipropyl- 8-(p-sulfophenyl)xanthine (DPSPX) to explore the effect of endogenous adenosine. Plasma epinephrine and norepinephrine levels in response to hydralazine-induced hypotension were measured in these animals. The same protocol was repeated in rats pretreated with either adrenalectomy or captopril. The results showed that DPSPX treatment significantly increased plasma epinephrine and norepinephrine levels at both baseline conditions and after hydralazine-induced hypotension. The results from the adrenalectomized rats showed that the difference in plasma epinephrine level between the control and DPSPX groups originated from the adrenal medulla. Pretreatment with captopril attenuated the rise of plasma epinephrine and norepinephrine levels in DPSPX-treated animals. This result suggests that endogenous adenosine receptors inhibit epinephrine release from the adrenal medulla and suppress plasma norepinephrine levels. When catecholamine release was stimulated by physiological and pharmacological stimuli, this inhibitory function of adenosine receptors was augmented. The renin-angiotensin system is at least partially responsible for the modulatory function of endogenous adenosine on the catecholamine response as demonstrated in this study.
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PMID:Modulatory effects of endogenous adenosine on epinephrine secretion from the adrenal medulla of the rat. 799 28

The purpose of this study was to test the hypothesis that endogenous adenosine suppresses noradrenergic neurotransmission during hemorrhagic hypotension. Rats were prepared for in situ blood-perfusion of their mesenteric vascular beds and received throughout the protocol an intramesenteric artery infusion of either saline (n = 14) or 1,3-dipropyl-8-(p-sulfophenyl)-xanthine (DPSPX, 40 micrograms/min; n = 14), an adenosine receptor antagonist. Vascular responses to periarterial sympathetic nerve stimulation (PNS; 3, 5 and 7 Hz) and to exogenous norepinephrine (NE; 100, 200 and 300 ng) were obtained at base-line and at 30, 75 and 120 min into hemorrhagic hypotension (arterial blood pressure = 50 mm Hg). Some experiments were conducted in rats without kidneys to prevent indirect modulation of neurotransmission by adenosine via the renin-angiotensin system. Vascular responses to PNS and NE were not significantly affected by DPSPX regardless of time into hemorrhagic hypotension, presence or absence of kidneys or stimulus intensity frequency of PNS or dose of NE). Hemorrhagic hypotension per se significantly (P < .0001) potentiated responses to PNS but did not significantly affect responses to NE. The effect of hemorrhage on responses to PNS was not significantly affected by DPSPX or nephrectomy and occurred similarly at all three levels of PNS. During hemorrhage, DPSPX treatment significantly increased PRA levels (P < .039) in rats with intact kidneys. These data indicate that endogenous adenosine inhibits renin release during hemorrhagic hypotension, but does not attenuate noradrenergic neurotransmission even during prolonged hemorrhagic hypotension. Finally, these experiments indicate that hemorrhagic hypotension can enhance noradrenergic neurotransmission by a mechanism that does not involve the renal renin-angiotensin system.
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PMID:Role of adenosine in noradrenergic neurotransmission during hemorrhagic hypotension. 807 51

Radiographic contrast media (CM) can induce renal failure and this may serve as an experimental model of acute renal failure (ARF). One vasoactive factor likely to be involved in ARF is adenosine. In a double-blind, placebo-controlled study we investigated the effect of theophylline (TP), an adenosine receptor antagonist, regarding changes in renal hemodynamics induced by CM. Thirty-nine patients who received 100 ml of a non-ionic low osmolar CM (iopromide) were studied for changes in GFR and RPF by continuous inulin and PAH clearance before and until four hours after CM application. Forty-five minutes before the application of CM, patients were randomized and received either theophylline (5 mg/kg body wt) or the vehicle and placebo (saline) intravenously in a blinded manner. We additionally measured the creatinine clearance on the day before and two days after CM application. Sodium excretion, N-acetyl-beta-glucosaminidase (NAG) excretion, plasma renin activity (PRA) and aldosterone levels were also measured before and after CM application. Theophylline levels were within the therapeutic range in patients of the theophylline group during and four hours after CM application (59.0 +/- 10.6 mumol/liter and 40.1 +/- 10.9 mumol/liter). GFR, measured by inulin clearance significantly declined under CM application in patients without TP application (N = 19; 88 +/- 40 to 75 +/- 32 ml/min/1.72 m2; P < 0.01). In the group of patients receiving theophylline (N = 18) the GFR remained constant (75 +/- 26 vs. 78 +/- 33 ml/min/1.72 m2).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine antagonist theophylline prevents the reduction of glomerular filtration rate after contrast media application. 807 55

Considerable attention has been focused on the purine nucleoside, adenosine, in the control of renal blood flow, epithelial transport, and renin secretion; however, surprisingly little attention has been directed toward the renal effects of purine nucleotides such as adenosine triphosphate (ATP). Recent studies utilizing in vivo micropuncture and in vitro techniques have demonstrated that renal vascular, epithelial, and mesangial cells respond to extracellular ATP via mechanisms distinct from those elicited by adenosine. ATP vasoconstricts afferent but not efferent arterioles whereas adenosine vasoconstricts both vascular segments. Adenosine-mediated afferent arteriolar vasoconstriction is abolished by adenosine receptor antagonists, whereas the response to ATP is enhanced. ATP-mediated vasoconstriction reaches a maximum within seconds of exposure while the vasoconstriction induced by adenosine develops more slowly. L-type calcium channel antagonists such as diltiazem or felodipine prevent the sustained afferent vasoconstriction produced by ATP. Data from micropuncture experiments indicate that peritubular capillary infusion of ATP reduces glomerular pressure and results in marked attenuation of the tubuloglomerular feedback mechanism, which transmits signals from the macula densa to the afferent arteriole. These data support the existence of ATP-sensitive P2 purinoceptors in the preglomerular microvasculature that contribute to the control of renal vascular function via activation of calcium channels.
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PMID:Extracellular ATP in the regulation of renal microvascular function. 814 38

Non-modulation has been proposed as an intermediate phenotype in human essential hypertension. The trait is characterized by blunted aldosterone and renal plasma flow responses to short-term angiotensin II (Ang II) infusion. Elevated tissue Ang II levels or decreased tissue adenosine levels could account for this decreased sensitivity to Ang II. In support of the latter possibility, endogenous adenosine has been shown to contribute to the renal vasoconstrictive response to Ang II in animals. We therefore tested the hypothesis that endogenous adenosine contributes to modulation of renal plasma flow in sodium-replete humans. We examined the effect of long-term administration of the adenosine receptor antagonist caffeine on baseline renal plasma flow and on the renal plasma flow response to short-term Ang II infusion in six salt-replete normotensive subjects in a single-blind, placebo-controlled study. para-Aminohippurate clearance was used to assess renal plasma flow. Ang II was infused in graded doses (0.3 to 3 ng/kg per minute) in the presence and absence of caffeine (250 mg PO TID for 7 days). Blood pressure, plasma renin activity, Ang II, electrolytes, and para-aminohippurate clearance were measured before and after each dose of Ang II. Caffeine did not alter either baseline blood pressure or the blood pressure response to Ang II but did increase baseline plasma renin activity from 0.72 +/- 0.09 to 1.42 +/- 0.26 ng angiotensin I/mL per hour (P = .01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Caffeine attenuates the renal vascular response to angiotensin II infusion. 824 16

Animals treated acutely with an adenosine receptor antagonist have elevated plasma renin activity. This observation suggests that endogenous adenosine plays a physiologically significant role in restraining renin release. However, it is unclear whether chronic blockade of adenosine receptors would cause a rise of renin activity since tolerance to adenosine blockade is known to develop quickly. An earlier study partially addressed this question by showing that chronic blockade of adenosine receptors with caffeine exacerbated both the rise of plasma renin activity and the decline of renal function in 2-kidney-1-clip (2K1C) renovascular hypertensive rats. However, that study did not determine whether the difference in renin activity occurred solely as a secondary result of the difference in renal function. The purpose of this study was to reexamine the effect of chronic caffeine consumption on plasma renin activity and angiotensin I levels in animals in another high-renin model, i.e., the low sodium diet. The low sodium diet is devoid of the potential confounding effect of deteriorating renal function associated with the 2K1C renovascular hypertension model. In this study, animals received normal rat chow and drank either 0.1% caffeine water or vehicle for ten days. After ten days, all rats were switched to a low sodium diet for three weeks. Plasma renin activity and plasma angiotensin I levels were measured before, and at 1 and 3 weeks after initiating the low sodium diet. The results of this study show that chronic blockade of adenosine receptors with 0.1% caffeine water increases plasma renin activity and angiotensin I concentration before and throughout the three weeks when animals were on the low sodium diet. The results of this study suggest that the inhibitory role of adenosine on renin release is a general physiological process, rather than a special situation applicable only to the 2K1C model.
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PMID:Effect of caffeine treatment on plasma renin activity and angiotensin I concentrations in rats on a low sodium diet. 844 83


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