Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven normotensive untreated patients with obstructive sleep apnea (OSA) and five control subjects without OSA were compared. Patients with cardiac dilation, chronic airflow limitation, liver and kidney disease, or diabetes mellitus were excluded. Change in pressure-heart rate relation to alpha-adrenergic stimulation (P-HRR), extracellular volume (ECV), and plasma volume (Vp) were measured during daytime. Plasma atrial natriuretic peptide (ANP), plasma renin and aldosterone concentrations were obtained at 1 hour intervals during the night. A mean apnea/hypopnea index (AHI) of 52.2 +/- 23.9/h and a mean lowest arterial oxygen saturation (SaO2) of 61.2 +/- 19.3% (mean +/- SD) were determined from polysomnographic monitoring in the patient group. Release of ANP was significantly higher during sleep in OSA patients than in control subjects (P < .01), with a maximum concentration between 4 and 6 AM in the former. Daytime ECV was significantly higher (P < .05) and Vp significantly lower (P < .05) in OSA patients. Night maximum concentration of ANP (max ANP) was negatively related to AHI (P < .05). P-HRR was negatively related to AHI (P < .05) and positively related to max ANP (P < .05). In conclusion, OSA syndrome alters hormonal system control of body fluid compartment regulation. The decreased response in night max ANP secretion in the most severe OSA patients could be explained by the smaller Vp observed in these patients, decreasing atrial and ventricular pressure loading. Furthermore, alteration of P-HRR, correlated to AHI and max ANP, strengthens the hypothesis that patients who develop hypertension are those in whom the protective mechanism of ANP release failed.
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PMID:Pressure-heart rate responses to alpha-adrenergic stimulation and hormonal regulation in normotensive patients with obstructive sleep apnea. 900 45

Renin binding protein (RnBP), a cellular renin inhibitor, has been identified as the enzyme N-acetyl-D-glucosamine (GlcNAc) 2-epimerase. Our recent studies demonstrated that rat GlcNAc 2-epimerase has a ten-times higher affinity for ATP, dATP, and ddATP than the human enzyme [Takahashi, S. et al. (2001) J. Biochem. 130, 815-821]. To identify the domain conferring nucleotide binding to GlcNAc 2-epimerase, we constructed a series of chimeric enzymes successively replacing the three domains of the human enzyme (N-terminal, middle, and C-terminal domains) with the corresponding domains of the rat enzyme. Chimeras were expressed in Escherichia coli JM109 cells under the control of the Taq promoter. The purified chimeric enzymes had GlcNAc 2-epimerase activity and inhibited renin activity in a dose-dependent manner. The recombinant human and rat enzymes required catalytic amounts of ATP with apparent K(m) values of 73 and 5.5 microM, respectively. Chimeric enzymes of HHR, RHH, and RHR (H, human type domain; R, rat type domain) had nearly the same nucleotide specificity as the human GlcNAc 2-epimerase. On the other hand, HRR, HRH, and RRH chimeras had the same nucleotide specificity as the rat enzyme. These results indicate that the middle domain of the GlcNAc 2-epimerase molecule participates in the specificity for and binding of nucleotides, and that nucleotides are essential to form the catalytic domain of the enzyme.
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PMID:Identification of a domain conferring nucleotide binding to the N-acetyl-d-glucosamine 2-epimerase (Renin binding protein). 1192 99

Recently, a receptor for renin was described that may be important for vascular uptake and activation of (pro)renin, thus leading to local generation of angiotensin II. To assess the in vivo relevance of this protein, we generated transgenic rats overexpressing the human renin receptor gene in smooth muscle tissue, under the control of a 16-kb fragment of the mouse smooth muscle myosin heavy chain gene [TGR(SMMHC-HRR)]. Four lines of transgenic animals were obtained. The correct pattern of expression of the transgene was confirmed by RNase protection assay and in situ hybridization. TGR(SMMHC-HRR) rats are fertile and develop normally. After 6 months of age, transgenic rats develop a cardiovascular phenotype with an elevated systolic blood pressure (137.8+/-5 versus 118.9+/-3.7 mm Hg; P=0.008), and an augmentation in heart rate (349.1+/-7.7 versus 303.1+/-16.16 bpm; P=0.023) in TGR(SMMHC-HRR) and controls, respectively. These alterations are progressively increasing with aging. Although kidney function and plasma renin were normal in TGR(SMMHC-HRR), an increase in plasma aldosterone [TGR(SMMHC-HRR) 428+/-64.9 versus 207.3+/-73.24 pg/mL in control; P=0.02] and in aldosterone/renin ratio [TGR(SMMHC-HRR) 8.04+/-2.2 versus 2.8+/-0.55 in control; P=0.03] was observed. This suggests that renin receptor overexpression has resulted in increased intraadrenal angiotensin II, thereby provoking enhanced aldosterone generation in the absence of changes in plasma renin. The rise in aldosterone may underlie, at least in part, the observed cardiovascular phenotype of TGR(SMMHC-HRR).
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PMID:Elevated blood pressure and heart rate in human renin receptor transgenic rats. 1640 65

We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated pulmonary arterial tension and pulmonary arterial pressure (PAP) in renal hypertensive rats (RHR) made by complete ligation of left renal artery. Losartan induced a depressor response that was smaller in RHR than in normotensive rats (NR) (3.3 and 7.0 mmHg, respectively, at 3.0 mg/kg, p<0.05), and the response was significantly reduced by N(G)-nitro-L-arginine methyl ester (L-NAME). Angiotensin II elevated the PAP (7.6 and 10.8 mmHg at 0.1 mug/kg; 20.3 and 23.6 mmHg at 1.0 mug/kg, respectively) and contracted the isolated pulmonary artery (pD(2): 8.79 and 8.71, respectively) from both NR and RHR with similar magnitude, and these effects were significantly enhanced by L-NAME in NR, but not in HRR. Acetylcholine lowered the PAP slightly less effectively in RHR than in NR (3.8 and 6.0 mmHg at 10 mug/kg, respectively) and relaxed the pulmonary artery precontracted with norepinephrine in both rats with similar magnitude (E(max): 60.8 and 63.6%, respectively), and the effect being completely abolished after pretreatment with L-NAME or removal of endothelial cells. These results suggest that nitric oxide interacts with renin angiotensin system to control the pulmonary vascular tension and pulmonary arterial circulation of RHR.
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PMID:Interaction of nitric oxide and renin angiotensin system in pulmonary arterial circulation of RHR. 1898 78