Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared the abilities of the adenosine antagonists caffeine and 8-(p-sulfophenyl)theophylline (8-SPT) to block adenosine receptor-mediated hypotension and bradycardia in anesthetized rats. Few quantitative data exist concerning the amounts of caffeine needed to prevent the cardiovascular effects of physiologic plasma adenosine concentrations or concerning the site of action (central or peripheral) of such blockade. Thus, dose-response curves were constructed for the antagonism by caffeine or 8-SPT of the hypotension and bradycardia caused by infusing adenosine i.v. or by giving bolus i.v. injections of the adenosine analogs 2-chloroadenosine, R-phenylisopropyladenosine or N-ethylcarboxamidoadenosine. We also quantitated the suppression by caffeine or 8-SPT of the ability of adenosine to potentiate nicotine-induced hypertension and tachycardia. Caffeine (EC50 = 92 microM) and 8-SPT (EC50 = 48 microM) blocked the hypotension produced by elevating plasma adenosine levels from 1.22 to 1.74 microM. Similar drug doses were needed to inhibit the potentiation by adenosine of pressor and chronotropic responses to nicotine or to antagonize the hypotensive and negative chronotropic effects of 2-chloroadenosine, R-phenylisopropyladenosine and N-ethylcarboxamidoadenosine. As expected, neither caffeine nor 8-SPT demonstrated selectivity for A1 (predominating at the heart) vs. A2 (predominating at blood vessels) receptor subtypes. Administration of as much as 50 mg/kg i.p. of 8-SPT failed to produce detectable brain levels of the drug, demonstrating its failure to gain access to the central nervous system and indicating that the site at which the drug antagonizes the cardiovascular effects of adenosine is peripheral.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antagonism of the cardiovascular effects of adenosine by caffeine or 8-(p-sulfophenyl)theophylline. 380 7

1. In seven unanaesthetized fetal sheep (> 80% term), isocapnic hypoxia (arterial partial pressure of O2, Pa,O2, approximately 15 mmHg) was induced for 1 h by lowering maternal inspired PO2. Fetal hypoxia was also produced during intra-arterial administration of the adenosine receptor antagonist 8-(p-sulphophenyl)-theophylline (8-SPT). The fetal 8-SPT infusion was begun just prior to hypoxia and was stopped when fetal Pa,O2 was returned to normal. 2. Hypoxia induced a progressive fetal acidosis, a rise in mean arterial pressure, a transient fall in heart rate and a decrease in breathing movements. 8-SPT significantly reduced the metabolic acidosis and abolished the hypertension and bradycardia without altering hypoxic inhibition of fetal breathing. Administration of the vehicle for 8-SPT during hypoxia did not significantly affect the normal fetal metabolic and cardiovascular responses to acute O2 deprivation. 3. It is concluded that adenosine mediates the fetal bradycardia and hypertension produced by hypoxia, indicating that adenosine modulates fetal autonomic responses to acute oxygen deficiency. Secondly, adenosine contributes to fetal metabolic acidaemia, suggesting that adenosine also modulates fetal glycolytic responses to hypoxia.
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PMID:Adenosine mediates metabolic and cardiovascular responses to hypoxia in fetal sheep. 857 65

Structural and mechanical properties of the arterial wall are altered in patients with renal failure. Age and hypertension are known to affect the vessel wall structure. Aging process of arterial wall appears to be accelerated in patients with end-stage renal failure. The mechanisms responsible for reduced arterial compliance and distensibility in dialyse patients and renal transplant recipients without hypertension remain to be evaluated. 20 normotensive dialyse patients (D), 20 normotensive renal transplant recipients (T) and 20 healthy volunteers (N) matched for age, sex and blood pressure as controls were enrolled in to the study. Patients with cardiovascular risk factors and diabetes were excluded. The arterial blood pressure of all patients placed below 140/90 mmHg. The dialyse patients and renal transplant recipients were eligible for the study if the serum creatinine level was below 2 mg/dl. In all subjects, fasting concentrations of serum creatinine, total cholesterol, HDL-cholesterol, LDL-cholesterol, hemoglobin and glucose were determined at enrollment to the study. Long-term immunosuppression consisted of cyclosporine and prednisolone. Blood pressure was measured using an automatic sphygmomanometer (Criticon Dinamap model 1846 SX). Pulse wave velocity (PWV) was evaluated using non-invasive automatic Complior device. The vessel wall properties of the left common carotid artery were studied using multigate pulsed Doppler's system (Pie Medical Equipment BV Maastricht, The Netherlands). The frequency of transducer used was 7.5 MHz. With this non-invasive method, the end-diastolic diameter (d) and the systolic increase of vessel diameter (distension delta d) were measured using ECG trigger. From these data relative systolic increase of vessel diameter (delta d/d) and arterial wall distensibility coefficient (DC) were calculated. Simultaneously with the ultrasound measurements at the left common carotid artery carotid pulse waveforms are recorded using applanation tonometry (Micro Tip Pulse Transducer, SPT 301 and Transducer Control Unit TCB-500, Millar Instruments, Houston, TX, USA). Systolic blood pressure (SBP) and central pulse pressure (CPP) were significantly higher in (T) than in (D) and (N) group respectively 139 +/- 18 mmHg and 58 +/- 16 mmHg vs 127 +/- 13 mmHg and 49 +/- 11 mmHg and 132 mmHg and 50 +/- 11 mmHg. The end-diastolic diameter (d) did not change significantly between all groups. The systolic increase of vessel diameter (distension delta d) was significantly lower in patients group (D) and (T) respectively 461 +/- 33 microm and 501 +/- 34 microm than in controls. Similar relative systolic increase of vessel diameter (delta d/d) was in these groups significantly lower than in healthy volunteers, respectively (D) 6.26 +/- 0.5%, (T) 6.91 +/- 0.4% vs (N) 9.14 +/- 0.4%. The distensibility coefficient were also significantly lower in (D) and (T) than in (N) groups respectively (D) 18.31 +/- 1.4 10(-3)/kPa and (T) 17.97 +/- 1.4 10(-3)/kPa and (N) 24.3 +/- 0.5 10(-3)/kPa. PWV in both groups of patients was statistically significant higher than in control group correspondingly (D) 11.2 +/- 1.02 m/s and (T) 12.8 +/- 1.12 m/s, (N) 9.5 +/- 0.88 m/s. There was significant correlation between the change of arterial DC, PWV and CPP in (T) group (n = 20; r = -0.42; p < 0.01 and n = 20; r = 0.47; p < 0.05). The arterial wall elastic properties in dialyse and renal recipients patients are decreased. End-stage renal disease accelerates arterial stiffening despite arteriosclerosis and hypertension. Renal transplantation do not reverse lost of elastic properties of arteries in end-stage renal insufficiency.
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PMID:[Large artery wall properties in dialyse and renal transplant patients with normal blood pressure]. 1586 37

Electroacupuncture (EA) can be used to lower high blood pressure (BP) in clinical practice. However, precise mechanisms underlying its effects on elevated BP remain unclear. Our previous studies have shown that EA at the P5-6 acupoints, overlying the median nerve, attenuates elevated BP induced by gastric distension (GD) through influence on rostral ventrolateral medulla (rVLM). Although adenosine is released during neuronal activation in the rVLM, its role in acupuncture-cardiovascular regulation is unknown. The purinergic system is involved in cardiovascular pressor and depressor responses, including via selective activation of A1 and A2 a rVLM receptors, respectively. The action of A2 a receptor stimulation in the central nervous system may be further regulated through an endogenous opioid mechanism. However, it is uncertain whether this putative action occurs in the rVLM. We hypothesized that adenosine in the rVLM contributes to EA modulation of sympathoexcitatory reflexes through an A2 a but not an A1 adenosine receptor-opioid mechanism. EA or sham-EA was applied at the P5-6 acupoints in Sprague-Dawley male rats subjected to repeated GD under anesthesia. We found that EA (n = 6) but not sham-EA (n = 5) at P5-6 significantly (P < 0.05) attenuated GD-induced elevations in BP. EA modulation of sympathoexcitatory cardiovascular reflexes was reversed significantly after rVLM microinjection (50 nl) of 8-SPT (10 mM; non-selective adenosine receptor antagonist; n = 7) or SCH 58261 (1 mM; A2 a receptor antagonist; n = 8; both P < 0.05), but not by DPCPX (3 mM; A1 receptor antagonist; n = 6) or the vehicle (5% dimethylsulfoxide; n = 6). Moreover, microinjection of an A2 a receptor agonist, CGS-21680 (0.4 mM; n = 8) into the rVLM attenuated GD-induced pressor responses without EA, which mimicked EA's inhibitory effects (P < 0.05). After blockade of opioid receptors with naloxone (1 mM) in the rVLM, SCH 58261's reversal of EA's effect on GD-induced pressor responses was blunted, and CGS-21680-mediated inhibitory effect on pressor responses was not observed. Furthermore, neurons labeled with adenosine A2 a receptors were anatomically co-localized with neurons stained with enkephalin in the rVLM. These data suggest that the involvement of rVLM adenosine A2 a receptors in EA modulation of GD-induced pressor reflexes is, at least in part, dependent on the presence of endogenous opioids.
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PMID:Adenosine Receptor A2a, but Not A1 in the rVLM Participates Along With Opioids in Acupuncture-Mediated Inhibition of Excitatory Cardiovascular Reflexes. 3163 31