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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine is a potent arterial vasodilator that, because of a short duration of action and acid lability, is ineffective in the oral treatment of hypertension. Y-341 is a synthetic adenosine analog that is acid stable and has a prolonged duration of action. It is highly selective for the A2 receptor, which is prevalent in the vascular smooth muscle and mediates vasodilation. To determine the efficacy of Y-341 as an antihypertensive agent, the effect of Y-341 on arterial pressure was studied in spontaneously hypertensive rats (SHR) in the awake state, 3 to 4 days after arterial cannulation. Y-341 (3 mg/kg) was dissolved in 5% DMSO and administered by gavage. Blood pressure and heart rate were monitored continuously at predetermined intervals. Fifteen minutes after administration, Y-341 reduced MAP from 180 +/- 4 to 126 +/- 2 mm Hg (n = 9, P < .001). There was no significant change in heart rate. The hypotensive effect was sustained over 8 h. Vehicle (n = 5) had no effect on blood pressure. The hypotensive effect was dose dependent when the dose of Y-341 was increased from 3 to 6 and 12 mg/kg. When Y-341 was administered at 3 mg/kg/day in a single dose for 5 consecutive days, there was no significant change in the magnitude of the hypotensive response over time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The hypotensive effect of an oral adenosine analog with selectivity for the A2 receptor in the spontaneously hypertensive rat. 766 28

The powerful vasoconstrictor autacoid thromboxane A2 (TxA2) has pathological roles in many diseases including pre-eclampsia or pregnancy induced hypertension (PIH). Adenosine and other purines are released by tissues during ischemia as occurs in the utero-placental circulation during PIH. These substances, particularly adenosine, may modulate TxA2 constrictor responses. We therefore characterized TxA2 receptors in the umbilical artery in vitro using the competitive antagonist GR32191. Also examined was the Ca2+ channels' involvement in adenosine-induced inhibition of TxA2 vasoconstriction. Results showed that TxA2 receptors on umbilical arteries are identical to those present in platelets, the placenta and umbilical vein. Adenosine was found to inhibit equally constriction involving either voltage or receptor operated Ca2+ channels.
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PMID:Modulation by adenosine of thromboxane A2 receptor-mediated constriction in the human umbilical artery. 795 95

Nerve growth factor (NGF) is a potent neurotrophin signaling protein, the best-known member of a family of similar neurotrophins. Specific neuronal populations depend upon the neurotrophins for normal function and disturbances in NGF and neurotrophin supply have been implicated in neurodegenerative disease, diabetes, and hypertension. This report details experiments in which the hourly pattern of NGF secretion by cultured vascular smooth muscle cells is examined. Vascular smooth muscle cells are major innervation targets of the neuronal population first discovered to be NGF-dependent: the sympathetic principal neurons. The results show that arginine vasopressin (AVP), angiotensin II (AngII), and alpha-adrenergic receptor activation, all contractile stimuli, elevate NGF secretion. However, AVP dependably does so alone while AngII requires coactivation of adenosine receptors. Adenosine alone inhibits secretion and the alpha-adrenergic increase in NGF output can be antagonized by activation of beta-adrenergic receptors. A change to fresh culture medium is also a potent stimulus to increased NGF output.
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PMID:Receptor-mediated stimulation and inhibition of nerve growth factor secretion by vascular smooth muscle. 839 98

The effects of adenosine and sodium nitroprusside (SNP) on central hemodynamics and myocardial blood flow and metabolism were investigated postoperatively after elective coronary artery bypass (CABG) surgery in ten sedated and mechanically ventilated patients in the intensive care unit. During three consecutive 15-min periods, SNP (0.8 +/- 0.1 micrograms.kg-1 x min-1), adenosine (88.9 +/- 13.3 micrograms.kg-1 x min-1), and then again SNP (0.7 +/- 0.1 micrograms.kg-1 x min-1) were infused to control postoperative hypertension at a mean arterial pressure of approximately 80 mm Hg. Systemic and pulmonary hemodynamics and global (coronary sinus flow, CSF) as well as regional (great cardiac vein flow, GCVF) myocardial blood flow and metabolic variables were measured. During adenosine infusion, in comparison to SNP, heart rate was unchanged, stroke volume index and cardiac index increased (24% and 32%, respectively), and the systemic vascular resistance index decreased (-26%). Mean pulmonary arterial pressure (24%) as well as pulmonary capillary wedge pressure (27%) and central venous pressure (18%) were higher with adenosine compared to SNP. Adenosine also increased CSF and GCVF (108% and 103%, respectively) without altering the CSF/GCVF flow ratio compared to SNP. Furthermore, adenosine increased the coronary oxygen content (51%) and decreased the arterio-great cardiac vein oxygen content difference (-48%) without changing regional myocardial oxygen consumption, indicating a more pronounced hyperkinetic myocardial circulation compared to SNP. In addition, adenosine infusion decreased arterial PO2 (-11%) and increased the intrapulmonary shunt fraction (57%). The PR interval time of the electrocardiogram was prolonged (12%) and the ST segment was more depressed during adenosine infusion compared to SNP.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Vasodilation with adenosine or sodium nitroprusside after coronary artery bypass surgery: a comparative study on myocardial blood flow and metabolism. 845 57

Adenosine has a major regulatory function in the heart and many tissues. Our previous work showed that a cytosolic (not a membrane, as previously hypothesized) 5'-nucleotidase from dog heart has the kinetic properties consistent with it being the enzyme responsible for adenosine formation from adenosine 5'-monophosphate (AMP) in response to hypoxia or ischemia. In the present study, we evaluated the spatial distribution of AMP-specific cytosolic 5'-nucleotidase in dog heart using electron microscopic immunogold localization. Polyclonal antibodies raised against purified cytosolic 5'-nucleotidase recognized the 43-kd subunit of the enzyme on Western blots of both purified enzyme and the soluble fraction of dog heart homogenates but did not react with proteins extracted from the membrane fraction. Purified cytosolic 5'-nucleotidase and 5'-nucleotidase activity present in the soluble fraction of heart homogenates were inhibited by anti-cytosolic 5'-nucleotidase, but the membrane fraction was not. The monospecific antibodies against the cytosolic 5'-nucleotidase were used for electron microscopic immunogold localization of cytosolic 5'-nucleotidase in dog heart tissue sections. Cytosolic 5'-nucleotidase was found in the cytoplasm of red blood cells, cardiac myocytes, and endothelium; the plasma membrane and interstitium were devoid of gold label. These results are the first to document the presence cytosolic 5'-nucleotidase in specific cell types in the heart and demonstrate the potential for these cell types to produce adenosine via cytosolic 5'-nucleotidase.
Hypertension 1993 Jun
PMID:Immunogold localization of adenosine 5'-monophosphate-specific cytosolic 5'-nucleotidase in dog heart. 850 99

Several endogenous factors generated within the vessel wall have been implicated in contributing to the vascular remodeling process associated with hypertension and atherosclerosis. Furthermore, substances generated by smooth muscle cells (SMCs) are known to regulate SMC proliferation in an autocrine fashion. Adenosine is a vasodilator synthesized by SMCs, and exogenous adenosine inhibits SMC proliferation. However, whether adenosine produced endogenously has antimitogenic effects is not known. Hence, we evaluated the effects of SMC-derived adenosine on 2.5% fetal calf serum-induced proliferation of rat aortic SMCs. SMC proliferation was assayed by measurement of DNA synthesis ([3H]thymidine incorporation) and cell counting. To determine the effects of endogenous adenosine on SMC proliferation, we stimulated growth-arrested SMCs with 2.5% fetal calf serum in the presence and absence of modulators of adenosine levels, including (1) erythro-9-(2-hydroxy-3-nonyl)adenine hydrochloride (EHNA; inhibits adenosine deaminase), (2) dipyridamole (blocks adenosine transport and inhibits phosphodiesterase), (3) dipyridamole plus EHNA, and (4) adenosine with or without EHNA. [3H]Thymidine incorporation and cell number were measured after 24 and 96 hours, respectively. EHNA and dipyridamole inhibited both FCS-induced DNA synthesis and cell proliferation in a concentration-dependent manner. Furthermore, extracellular (in medium) adenosine levels were significantly increased when cultured cells were treated with EHNA, and the inhibitory effects of dipyridamole as well as exogenous adenosine were enhanced in the presence of EHNA. Additionally, the inhibitory effects of dipyridamole and EHNA on DNA synthesis were significantly reduced in the presence of KF17837, an A2 adenosine receptor antagonist. These results indicate that SMC-derived adenosine can inhibit SMC proliferation. Hence, it is possible that a defect in localized adenosine synthesis within the vessel wall could contribute to vascular thickening and neointima formation.
Hypertension 1996 Mar
PMID:Smooth muscle cell-derived adenosine inhibits cell growth. 861 38

We previously reported that adenosine elicited site-dependent neuronal and cardiovascular responses in two subareas of the nucleus tractus solitarius (NTS) of normotensive rats. Pressor and tachycardic responses were obtained from the rostral NTS (adenosine pressor system), and depressor and bradycardic responses were obtained from the caudal NTS (adenosine depressor system). In both areas, adenosine inhibited the firing rate of barosensitive neurons. The present study investigated whether spontaneously hypertensive rats (SHR) exhibit abnormal neuronal and cardiovascular responses mediated by the adenosine pressor and depressor systems within the NTS. Male SHR and Wistar-Kyoto rats (WKY) were anesthesized with urethane and prepared for blood pressure and heart rate recording, stereotaxic microinjection of adenosine into the NTS, and extracellular recording of single-unit neuronal activity of NTS neurons. Chemical identification of the targeted neuronal pool was made by L-glutamate (5 nmol) and confirmed by histology. SHR exhibited significantly higher mean arterial pressure and firing rate of caudal NTS neurons (45.0 +/- 4.5 versus 27.3 +/- 4.7 spikes per 2.5 seconds, P <.05) but similar heart rate and neuronal firing rate of rostral NTS neurons compared with WKY. Adenosine (0.1, 1, and 10 nmol) elicited dose-related neuronal and cardiovascular responses in both strains. However, SHR exhibited differential alterations in both adenosine systems. Compared with WKY, SHR exhibited attenuated pressor, tachycardic, and neuronal responses mediated by the adenosine pressor system and exaggerated depressor, bradycardic, and neuronal responses mediated by the adenosine depressor system. In both strains, the responses elicited by adenosine were virtually abolished by theophylline (10 mg/kg IV), suggesting that these responses were mediated by adenosine receptors in the NTS. Furthermore, the theophylline-evoked increase in blood pressure was twofold higher in SHR (15.0 +/- 1.7 versus 6.9 +/- 1.5 mm Hg, P <.05); larger but nonsignificant increases in heart rate and neuronal firing rate also were evident in SHR compared with WKY. These findings suggest differential alterations in adenosine pressor and depressor systems in the NTS of SHR, which may be implicated in the pathophysiology of this model of hypertension.
Hypertension 1996 Apr
PMID:Differential alteration of neuronal and cardiovascular responses to adenosine microinjected into the nucleus tractus solitarius of spontaneously hypertensive rats. 861 72

Adenosine is produced locally in the kidney. Accumulating data suggest that adenosine plays a role in regulating renal functions. Using a microdialysis technique, we monitored adenosine levels in cortical and medullary renal interstitial fluid and urine after 5 days of diets containing low (0.15%), normal (0.28%), and high (4.0%) sodium. Samples were collected from anesthetized rats (n=5 for each diet). Microdialysis fluid was infused at a rate of 1 microL/min. Adenosine, measured by radioimmunoassay, was stable in the dialysate. During normal sodium intake, renal interstitial fluid adenosine estimated from the concentration in dialysate leaving the cortex was 63 +/- 6 nmol/L, which was significantly lower than in dialysate leaving the medulla (157 +/- 6 nmol/L, P<.01). The concentration of interstitial medullary adenosine was estimated to be 190 nmol/L. In rats consuming a low sodium diet, renal cortical and medullary dialysate adenosine concentrations were significantly decreased (P<.01) by 62.6% and 64.9%, respectively. Rats consuming a high sodium diet had renal cortical and medullary dialysate adenosine concentrations that were increased 18.2- and 18.9-fold, respectively (P<.01), compared with levels in rats on a low sodium diet. Similar to changes in dialysate adenosine, urinary adenosine concentration decreased during low sodium intake (P<.01) and increased during high sodium intake (P<.01). The higher adenosine levels in renal medullary than in cortical interstitial fluid may reflect its major renal site of generation. The changes in renal adenosine generation with sodium intake may reflect renal energy expenditure.
Hypertension 1996 Mar
PMID:Sodium intake markedly alters renal interstitial fluid adenosine. 869 45

1. The effect of long-term antagonism of P1-purinoceptors on vascular function was examined in the perfused mesenteric arterial bed isolated from rats which had received constant infusion of either the non-selective P1-purinoceptor antagonist, 1-3-dipropyl-8-sulphophenylxanthine (DPSPX, 30 micrograms kg-1 h-1, i.p.) or saline for seven days. Sympathetic and sensory-motor neurotransmission, smooth muscle and endothelial function were assessed. 2. Basal tone was similar in mesenteric arterial preparations from control and DPSPX-treated rats. Continuous perfusion with methoxamine (7-70 microM) induced similar increases in tone in control and DPSPX-treated preparations. In the presence of guanethidine (5 microM), electrical field stimulation (EFS; 1-12 Hz, 60V, 0.1 ms, 30 s) elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. In tissues from DPSPX-treated rats the nerve-mediated vasodilator responses were markedly augmented at all frequencies. Maximal relaxation at 8 Hz was 38.34 +/- 4.76% (n = 5) in controls and 65.92 +/- 3.68% (n = 5) after DPSPX-treatment (P < 0.01). Adenosine (3 microM) inhibited the frequency-dependent sensory-motor neurotransmission similar in preparations from controls and DPSPX-treated rats. 3. In raised-tone preparations calcitonin gene-related peptide (CGRP; 5,15 and 50 pmol), the principal vasodilator transmitter of sensory-motor nerves in rat mesenteric arteries, produced similar relaxations in control and DPSPX-treated preparations. Vasodilator responses to the sensory neurotoxin capsaicin (50 and 500 pmol) were also similar between the groups. 4. Assay of tissue CGRP levels of the superior mesenteric artery by enzyme-linked immunosorbent assay showed no significant difference in tissue levels of CGRP in controls, 120.25 +/- 26.34 pmol g-1 tissue (n = 6) and with DPSPX-treatment, 82.12 +/- 24.42 pmol g-1 tissue (n = 6). 5. In raised-tone preparations dose-dependent endothelium-dependent vasodilatation to acetylcholine and ATP, and endothelium-independent vasodilatation to sodium nitroprusside were similar in control and DPSPX-treated preparations. 6. EFS (4-32 Hz, 90V, 1 ms, 30 s) elicited frequency-dependent vasoconstriction due to activation of sympathetic nerves which was similar in controls and in DPSPX-treated preparations. Adenosine (10 and 30 microM) inhibited sympathetic neurotransmission similarly in control and DPSPX-treated preparations. Dose-dependent vasoconstriction to noradrenaline (NA) and ATP, and to KCI (0.15 mmol) was similar between the groups. 7. High performance liquid chromatographic analysis of tissue NA showed no significant difference in NA content of the superior mesenteric artery from DPSPX-treated (1.38 +/- 0.09 ng mg-1, n = 6) and control rats (1.46 +/- 0.17 ng mg-1, n = 6). 8. In conclusion, in rats with hypertension due to 7 days treatment with the P1-purinoceptor antagonist, DPSPX, there is an increase in sensory-motor vasodilatation of the mesenteric arterial bed. There is no change in sympathetic nerve, endothelial or smooth muscle function. Augmented sensory-motor neurotransmission, which does not involve a change in postjunctional responsiveness to CGRP or in the CGRP content of sensory-motor nerves, could be a compensatory change in response to the DPSPX- induced hypertension.
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PMID:Augmented sensory-motor vasodilatation of the rat mesenteric arterial bed after chronic infusion of the P1-purinoceptor antagonist, DPSPX. 884 31

Adenosine mechanisms are altered in brain stem nuclei associated with cardiovascular control in spontaneously hypertensive rats (SHR). Therefore, in the present study we used a number of techniques to compare the binding of the adenosine transport inhibitor [3H]nitrobenzylthioinosine ([3H]NBMPR) as well as adenosine deaminase immunoreactivity (ADA-IR) in brain stems and nodose ganglia of SHR and age-matched normotensive Donryu rats (DRY). Saturation binding revealed a single class of [3H]NBMPR binding sites in the dorsal brain stem of both strains, with Kd and Bmax values of 65 +/- 9 pmol/L and 282 +/- 31 fmol/mg protein, respectively, in SHR and 129 +/- 2 pmol/L and 217 +/- 23 fmol/mg protein in DRY. The Kd for [3H]NBMPR was significantly lower in SHR than in DRY. In competition assays, NBMPR, dilazep, dipyridamole, and adenosine displaced [3H]NBMPR binding, with Kd values of 0.21 +/- 0.04, 57.16 +/- 16.20, 1340 +/- 100, and 87000 +/- 12500 nmol/L, respectively, in DRY and 0.17 +/- 0.04, 28.24 +/- 3.60, 621 +/- 100, and 32000 +/- 6820 in SHR. Kd values for all displacers were lower in SHR; however, only values for dipyridamole and adenosine reached statistical significance. Autoradiography of adenosine transport sites with [3H]NBMPR revealed that unilateral nodose ganglionectomy reduced [3H]NBMPR binding on the denervated side of the nucleus tractus solitarius by 20.6 +/- 1.1% in DRY and 18.7 +/- 2.3% in SHR. The density of [3H]NBMPR binding in nodose ganglia was significantly lower in SHR (0.99 +/- 0.06 Bq/mm2) than in DRY (1.25 +/- 0.08). Immunohistochemical studies demonstrated ADA-IR in the dorsal vagal complex, associated with both nerve cells and fibers. Measurement of ADA-IR in the dorsal vagal complex with an 125I-labeled secondary antibody revealed a significantly higher level of ADA-IR in SHR (122%) than in DRY. In the nodose ganglia, ADA-IR was associated with a population of vagal perikarya. The present study helps provide a molecular explanation for the previously reported impaired cardiovascular responses to intra-nucleus tractus solitarius microinjection of adenosine in hypertensive rats.
Hypertension 1996 Dec
PMID:Markers of adenosine removal in normotensive and hypertensive rat nervous tissue. 895 92


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