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

The effects of dipyridamole infusion on fetal arterial plasma adenosine level, [ADO], and the systemic cardiovascular system were studied in 10 fetal sheep at 130-135 days gestational age. Dipyridamole (0.25 mg/kg) was infused into the fetuses intravenously during normoxia and hypoxia. Plasma [ADO] was measured using high-performance liquid chromatography, (HPLC), and fetal heart rate and arterial blood pressure were monitored throughout the study. These studies were performed in the absence and presence of theophylline, an adenosine receptor antagonist. During normoxia (PO2, 23.8 +/- 2.0 Torr), dipyridamole infusion increased fetal plasma [ADO] from 0.82 +/- 0.10 microM to 1.41 +/- 0.16 microM within 1 min (P < 0.01) and fetal heart rate from 157 +/- 6 bpm to 174 +/- 7 bpm (P < 0.01), but did not change mean blood pressure. Fetal plasma [ADO] and fetal heart rate returned to basal levels quickly. Treatment with theophylline did not alter the elevation of plasma [ADO] after dipyridamole infusion, but abolished responses of fetal heart rate to dipyridamole infusion. After 15 min of hypoxia with an average arterial PO2 of 15.4 +/- 1.1 Torr, fetal plasma [ADO] increased to 1.15 +/- 0.14 microM (P < 0.01). Dipyridamole infusion then further raised fetal plasma [ADO] to 1.67 +/- 0.27 microM (P < 0.01). The duration of the increase of fetal plasma [ADO] after dipyridamole infusion was no longer in hypoxia than in normoxia, however there was no significant change in the pattern of transient fetal bradycardia and persistent hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Plasma adenosine and cardiovascular responses to dipyridamole in fetal sheep. 130 95

Adenosine is an inhibitory neuromodulator in several brain regions. In the nucleus tractus solitarius (NTS), however, adenosine exerts excitatory cardiovascular effects. The purpose of the present study was to elucidate the involvement of other endogenous mechanisms that could contribute to the final hemodynamic response to adenosine in this nucleus. In normotensive Sprague-Dawley rats, intra-NTS microinjection of adenosine (2.3 nmol/60 nl) decreased blood pressure and heart rate. These effects were blocked by prior administration of the specific adenosine receptor antagonist 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol) and by the two glutamate receptor antagonists kynurenic acid and glutamic diethylester. The specificity of the adenosine-glutamate interaction in the NTS was demonstrated with adrenergic and angiotensin receptor antagonists that did not affect the adenosine response and by experiments with glutamate receptor antagonists that did not affect nicotine actions in the NTS. Furthermore, an increase in glutamate levels was demonstrated during perfusion of adenosine through a microdialysis probe in the NTS of anesthetized rabbits. These findings indicate that adenosine increases the release of glutamate in the NTS and, thus, are at variance with the concept of a "universal" inhibitory effect of adenosine in the central nervous system.
Hypertension 1991 Oct
PMID:Cardiovascular excitatory effects of adenosine in the nucleus of the solitary tract. 168 Aug 12

Previous studies strongly suggest that adenosine receptors on juxtaglomerular cells function to restrain the secretion of renin induced by a variety of stimuli. The clinical significance of this is that caffeine, a widely consumed adenosine receptor antagonist, could augment renin release responses to diseases such as renovascular hypertension, liver cirrhosis and heart failure and to therapeutic maneuvers such as salt restriction, diuretics and vasodilators. Caffeine may be particularly troublesome in this regard because this methylxanthine has central nervous system effects and intracellular actions that also might contribute to the overall ability of caffeine to potentiate renin secretion. The purpose of this study was to document the effects of caffeine on renin release responses to a vasodilator and to investigate what mechanisms were responsible for any augmentation of vasodilator-induced renin secretion. Accordingly, we compared the effects of caffeine vs. 1,3-dipropyl-8-p-sulfophenylxanthine (DPSPX; a xanthine that we documented in this study not to significantly enter the brain or penetrate cell membranes) on base-line and hydralazine-induced renin release in both normal and beta adrenoceptor-blocked (propranolol, 15 mg/kg) rats. Both xanthines (at a dose of 10 mg/kg plus 150 micrograms/min) attenuated adenosine-mediated hypotension and bradycardia, and DPSPX was at least as effective as caffeine in antagonizing peripheral adenosine receptors. Caffeine and DPSPX increased base-line plasma renin activity to a similar extent regardless of whether the animals were pretreated with propranolol. In rats with an intact beta adrenergic system, caffeine, but not DPSPX, increased the renin release response to low-dose hydralazine (1 mg/kg). Although both xanthines augmented the renin release response to high-dose hydralazine (10 mg/kg), caffeine was more efficacious in this regard. In beta adrenoceptor-blocked rats, neither caffeine nor DPSPX augmented the renin release response to low-dose hydralazine, whereas both xanthines equally potentiated the renin release response to high-dose hydralazine. These data demonstrate that caffeine increases base-line renin release primarily by blocking peripheral (most likely renal), cell-surface adenosine receptors; however, caffeine potentiates vasodilator-induced renin secretion in part by blocking peripheral (most likely renal), cell-surface adenosine receptors and in part by additional central nervous system and/or intracellular mechanism(s) that involve the beta adrenergic system.
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PMID:Caffeine potentiates vasodilator-induced renin release. 200 84

We have investigated whether the insulin resistance reported to occur in hypertension is due to decreased insulin receptors or to adenosine receptors in adipocyte membranes. Membranes were isolated from adipocytes from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKy) rats and assayed for insulin receptors and A1 adenosine receptors. The two groups of membranes bound 125I-insulin equally, but in contrast the SHR membranes bound approximately 25% less 125I-HPIA ([(-)-N6-p-hydroxyphenylisopropyl adenosine], an A1 adenosine receptor agonist) than the WKy (P less than .005). Scatchard analysis demonstrated that this was due to a lower number of receptors in the SHR. The affinity of the receptor for HPIA was approximately 0.7 nmol/L in both groups. 5'-Nucleotidase activity was approximately 40% higher in membranes from SHR than WKy (P less than .001), indicating that adipocytes from SHR have a higher capacity for adenosine production. This may cause increased adenosine concentrations in the SHR adipose tissue, leading to adenosine receptor down-regulation. Since we have previously demonstrated that adenosine receptor down-regulation can lead to insulin resistance, these findings may partly account for the insulin resistance of hypertension.
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PMID:Decrease in A1 adenosine receptors in adipocytes from spontaneously hypertensive rats. 224 76

A limited occipital craniotomy was conducted on urethane-anesthetized, spontaneously breathing rats to expose the caudal medulla in the region of the obex. Microinjections of 5'-N-ethylcarboxamidoadenosine (NECA), an adenosine analog, were made into the medial region of the caudal nucleus tractus solitarius (NTS) at the level of the caudal tip of the area postrema, an area of the NTS in which there is known to be a functional co-existence of cardiovascular and respiratory-related neuronal elements. Cardiorespiratory responses were subsequently recorded for a 60 min test period. Microinjections of NECA, in the dose range of 0.35-350 pmol per rat, produced significant dose-related reductions in respiratory rate which were accompanied by dose-dependent increases in tidal volume and these pronounced effects on respiration persisted throughout the test period. In contrast, the effects of NECA microinjections on cardiovascular parameters in this region of the NTS were bidirectional and elicited considerably more complex responses during the test period. During the initial period (2-5 min) following injection, NECA elicited significant hypotension (at lower doses) and pressor responses (at higher doses) in addition to significant bradycardia (at lower doses) whereas by the end of the 60 min test period, almost all doses of NECA had resulted in hypertension and tachycardia. Multivariate analysis of variance (MANOVA) and correlation statistics indicated that the effects of NECA on blood pressure during the initial 2-5 min were dose-dependent and unlikely related to depression of respiratory frequency. A further examination of the data by MANOVA indicated that the pharmacological effects of NECA during the 60 min test period exhibited a highly significant and specific dose-dependent and time-related response pattern for the respiratory, but not the cardiovascular, parameters. Taken together, these manifold response patterns suggest that the respiratory effects of NECA may be mediated by different intrinsic mechanisms in the NTS than are the cardiovascular effects of NECA. At the end of the 60 min test period following the administration of NECA, the respiratory rate remained profoundly depressed. In view of previous studies showing that microinjections of cyclic AMP analogs, forskolin, isoproterenol and adenosine into the same NTS sites elicit a similar depression of respiration, the results with NECA in the present study further support the notion that cyclic AMP may serve as a second messenger in NTS respiratory control regions and these respiratory depressant effects may be mediated by a single adenosine receptor subtype.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Cardiorespiratory function is altered by picomole injections of 5'-N-ethylcarboxamidoadenosine into the nucleus tractus solitarius of rats. 233 63

In a previous study we discovered that the adenosine receptor antagonist, caffeine, increases plasma renin activity and blood pressure in renin-dependent renovascular hypertension. The purpose of the present investigation was to determine whether methylxanthines augment the increase in renin secretion induced by a reduction in renal perfusion pressure and, if so, whether this effect is mediated by a direct action on juxtaglomerular cells. Accordingly, we examined the effects of infusions of caffeine and theophylline directly into the renal artery on the increase in renin secretion induced by suprarenal aortic constriction. All studies were conducted in dogs receiving an intravenous infusion of propranolol to prevent changes in renin secretion mediated indirectly via the sympathetic nervous system. Caffeine (5 mg/min) increased the renin response to suprarenal aortic constriction about 10-fold without significantly affecting renal hemodynamics or excretory function. Theophylline (5 mg/kg), on the other hand, did not significantly increase the renin response to a reduction in renal perfusion pressure, but did increase urine flow and sodium excretion about 10-fold. However, in the non-filtering, beta-adrenoceptor blocked, canine kidney, theophylline markedly increased the renin response to suprarenal aortic constriction. These results indicate that methylxanthines can potentiate the renin response to a reduction in renal perfusion pressure most likely by directly affecting the juxtaglomerular cells; however, since increased sodium delivery to the macula densa inhibits renin release, the extent to which methylxanthines affect the renin response to renal artery hypotension depends on how vigorous the diuretic response is to a given methylxanthine.
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PMID:Methylxanthines augment the renin response to suprarenal-aortic constriction. 257 Mar 68

Adenosine acts at many sites to modulate neuronal activity. The purpose of this study was to investigate a possible role for adenosine as a neuromodulator of brainstem cardiovascular control. Microinjections of adenosine (0-2.3 nmol) were made stereotaxically into various brainstem sites. Injection of adenosine into the nucleus tractus solitarii (NTS) produced dose-related decreases in heart rate and systolic and diastolic blood pressures. Maximal changes occurred 90 seconds after injection. Injection into the area postrema also produced decreased heart rate and systolic and diastolic blood pressures. No significant effect occurred following injection into the C1 area. Adenosine 5'-triphosphate and its analogue, beta, gamma-methylene adenosine 5'-triphosphate also produced dose-related and potent vasodepressor and bradycardia effects in the NTS. Injection of 1,3-dipropyl-8-p-sulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist, produced no effect itself, but abolished for 45 minutes the actions of further injections of adenosine and adenosine 5'-triphosphate (but not L-glutamate) in both the NTS and area postrema. Thus, NTS and area postrema injections of adenosine decrease blood pressure and heart rate in anesthetized normotensive rats through adenosine receptors located in these areas. These findings support a role for endogenous adenosine as a central modulator in cardiovascular control.
Hypertension 1988 Feb
PMID:Purinergic receptors in the brainstem mediate hypotension and bradycardia. 327 13

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

The newly developed radiotelemetry system offers a number of advantages for the measurement of blood pressure and heart rate in laboratory animals. However, no available statistical methods permit valid use of the many data gathered with this continuous recording of hemodynamic parameters. This study describes elaboration and testing of mathematical functions as applied to the measurement of the effects of drugs on blood pressure and heart rate in spontaneously hypertensive rats. We used parametric functions analogous to those for pharmacokinetic studies. Curve fitting is in fact the only approach that provides reasonable estimates of hemodynamic kinetic constants. Nonlinear functions were assessed by analyzing telemetric hemodynamic effects induced by three adenosine receptor agonists with different selectivity for the A1 or A2a receptor. After acute administration in conscious rats, the A1 agonist 2-chloro-N6-cyclopentyladenosine induced dose-related hypotension (eg, 0.03 mg/kg; peak, -70 mm Hg; time to peak, 0.34 hour) and bradycardia (eg, 0.03 mg/kg; peak, -186 beats per minute [bpm]; time to peak, 0.38 hour). The A2a agonist 2-hexynyl-5'-N-ethylcarboxamidoadenosine induced dose-related hypotension (eg, 0.003 mg/kg; peak, -36 mm Hg; time to peak, 0.32 hour) with reflex tachycardia (eg, 0.003 mg/kg; peak, 152 bpm; time to peak, 0.35 hour). The nonselective adenosine agonist 5'-N-ethylcarboxamidoadenosine (0.1 mg/kg) induced hypotension (peak, -75 mm Hg; time to peak, 2.2 hours) and bradycardia followed by tachycardia (first peak, -131 bpm; time to peak, 1.26 hours; second peak, 123 bpm; time to peak, 13.9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1995 Apr
PMID:Modeling hemodynamic profiles by telemetry in the rat. A study with A1 and A2a adenosine agonists. 772 99

We previously reported that adenosine has significant depressor effects in the nucleus tractus solitarii and area postrema of the rat. The purpose of this study was to determine whether the spontaneously hypertensive rat (SHR) has abnormalities in medullary sensitivity to adenosine. Male SHR and Wistar-Kyoto (WKY) rats (aged 12 to 15 weeks) were anesthetized with urethane, and blood pressure was monitored intraarterially. Stereotaxic microinjection (60 nL) of adenosine was made into the nucleus tractus solitarii and the area postrema and was confirmed histologically. Dose-related decreases in mean blood pressure and heart rate occurred in both strains tested, and this effect was completely abolished by 1,3-dipropyl- 8-p-sulfophenylxanthine (0.92 nmol), a potent adenosine receptor antagonist. However, there were significant differences between SHR and WKY rats in the magnitude of blood pressure and heart rate depression. A similar pattern of response was found in the area postrema. Thus, adenosine is a potent depressor agent in the nucleus tractus solitarii and area postrema of rats, and adenosine has significantly fewer depressor effects in SHR. These data suggest that alterations in purinergic mechanisms of central cardiovascular control exist in the SHR model.
Hypertension 1995 Feb
PMID:Attenuated cardiovascular response to adenosine in the brain stem nuclei of spontaneously hypertensive rats. 784 79


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