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Hypotensive Response (hypotensive + response)
Selected AbstractsRole of Myocardial Contractility and Autonomic Control in the Hypotensive Response to a Limited Access Ethanol Paradigm in SHRsALCOHOLISM, Issue 6 2007Mahmoud M. El-Mas Background: Previous experimental studies that evaluated the chronic hemodynamic effect of ethanol employed the continuous exposure protocol of ethanol, which does not mimic the pattern of alcohol consumption in humans. This study dealt with the long-term hemodynamic and cardiovascular autonomic effects of ethanol, in a limited-access regimen in telemetered spontaneously hypertensive rats (SHRs). Methods: Changes in blood pressure (BP), heart rate (HR), myocardial contractility (dP/dtmax), and spectral cardiovascular autonomic profiles during the ethanol exposure period (2.5 or 5% w/v, 8 h/d, 8:30 am till 4:30 pm) were followed for 12 weeks. Results: Compared with control pair-fed SHRs, body weight and urine output, osmolality, and potassium levels were decreased in SHRs receiving 5% but not 2.5% ethanol. Blood pressure showed progressive falls during ethanol-feeding periods with a maximum effect observed at week 5. The peak hypotensive effect was maintained thereafter in SHRs receiving 5% ethanol in contrast to steady rises in BP in the 2.5% ethanol group to near-control levels by the conclusion of the study. Heart rate was slightly but significantly increased by ethanol 5% whereas dP/dtmax showed persistent reductions. Power spectral analysis showed that ethanol attenuated the baroreflex gain of HR as suggested by the reductions in index ,, the spectral index of spontaneous baroreflex sensitivity (BRS). Conclusions: It is concluded that limited access ethanol drinking in SHRs elicited hypotension that was concentration dependent and mediated, at least partly, through reductions in myocardial contractility. Baroreflex sensitivity attenuation by ethanol appeared to have limited the tachycardic response to ethanol and perhaps its capacity to offset the evoked hypotension. [source] Impact of nadir lower oesophageal sphincter pressure on bolus clearance assessed by combined manometry and multi-channel intra-luminal impedance measurementNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2010N. Q. Nguyen Abstract, This study aimed to assess the relationship between nadir lower oesophageal sphincter pressure (LOSP) and wave amplitude (WA) in oesophageal bolus clearance. Concurrent oesophageal manometry and impedance were performed in 146 subjects [41 healthy, 24 non-obstructive dysphagia (NOD) and 81 gastro-oesophageal reflux (GOR)]. Patients with achalasia and diffuse oesophageal spasm were excluded. Swallow responses were categorized by nadir LOSP. For each category of nadir LOSP, WA at the distal 2 recording sites were grouped into bins of 10 mmHg and the proportion of waves in each bin associated with a normal bolus presence time (BPT) was determined. Nadir LOSP, distal BPT, total bolus transit time and the proportion of impaired oesophageal clearance in patients with NOD were greater than those of healthy subjects and patients with GOR. Overall, responses with impaired oesophageal clearance had significantly lower WA (54 ± 1 vs 81 ± 1 mmHg; P < 0.0001) and higher nadir LOSP (2.7 ± 0.4 vs 1.0 ± 0.1 mmHg, P < 0.001). For each level of nadir LOSP, there was a direct relationship between distal WA and successful bolus clearance of both liquid and viscous boluses from the distal oesophagus. As nadir LOSP increased, the relationship between WA and bolus clearance shifted to the right and higher amplitudes were required to achieve the same effectiveness of clearance. Hypotensive responses with nadir LOSP ,3 mmHg were less likely to clear than those with nadir LOSP <3 mmHg, for both liquid (7/29 vs 162/276; P < 0.001) or viscous boluses (11/46 vs 176/279; P < 0.0001). Nadir LOSP is an important determinant of bolus clearance from the distal oesophagus, particularly in patients with NOD. [source] Cardiovascular effects of cannabinoids in conscious spontaneously hypertensive ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2007A J Wheal Background and purpose: In anaesthetized spontaneously hypertensive rats (SHR), there is evidence for up-regulation of cannabinoid (CB1) receptors: antagonism of CB1 receptors causes a rise in blood pressure, and administration of the endocannabinoid, anandamide, or inhibition of anandamide degradation causes hypotension. These findings have led to the suggestion that the endocannabinoid system may be a therapeutic target in hypertension. However, since the cardiovascular responses to cannabinoids are substantially influenced by anaesthesia, the purpose of this study was to assess regional haemodynamic responses to cannabinoid receptor stimulation and inhibition in conscious SHR. Experimental approach: Cardiovascular responses to i.v. administration of anandamide, the cannabinoid receptor agonist, WIN 55212-2, and the CB1 receptor antagonist, AM 251, were measured in male SHR, Wistar Kyoto rats and outbred Wistar rats, chronically instrumented for recording renal, mesenteric and hindquarters haemodynamics in the conscious, freely-moving state. Key results: Hypotensive responses to anandamide and WIN 55212-2 only occurred in SHR, but these were relatively modest and not associated with CB1 receptor-mediated vasodilatation. In SHR only, anandamide caused bradycardia, which was inhibited by AM 251. Furthermore, a pressor response to CB1 receptor antagonism occurred only in SHR, but was not associated with vasoconstriction. Moreover, there was some evidence for CB1 receptor-mediated vasoconstrictor actions of anandamide in SHR, which was not seen in the normotensive strains. Conclusions and implications: The results are consistent with activation of CB1 receptors in SHR by endogenous ligands exerting an antihypertensive effect, but the findings do not indicate enhanced CB1 receptor-mediated vasodilator mechanisms in SHR. British Journal of Pharmacology (2007) 152, 717,724; doi:10.1038/sj.bjp.0707410; published online 13 August 2007 [source] Possible mechanisms of action of the neutral extract from Bidens pilosa L. leaves on the cardiovascular system of anaesthetized ratsPHYTOTHERAPY RESEARCH, Issue 10 2003T. Dimo Abstract The aim of this study was to investigate the hypotensive and cardiac effects of the neutral extract from Bidens pilosa leaves. Intravenous administration of the extract resulted in a biphasic dose-related hypotensive activity. In normotensive rats (NTR), B. pilosa decreased systolic blood pressure by 18.26%, 42.5% and 30% at doses of 10, 20 and 30 mg/kg, respectively. In spontaneously hypertensive rats (SHR), the decrease in systolic blood pressure was 25.77%, 38.96% and 28.64% at the above doses, respectively. These doses induced hypotension by 27%, 34.13% and 18.73% respectively in salt-loaded hypertensive rats. In NTR, B. pilosa reduced heart rate by 23.68% and 61.18% at doses of 20 and 30 mg/kg, respectively. The force of contraction of the heart was only affected at 30 mg/kg. The initial phase of hypotensive response was partially inhibited by atropine while propranolol increased this effect. These results suggest that B. pilosa exhibited its ,rst hypotensive effects by acting on the cardiac pump ef,ciency and secondly through vasodilation. [source] Effects of histamine receptor blockade on cardiovascular changes induced by 35 GHz radio frequency radiation heatingAUTONOMIC & AUTACOID PHARMACOLOGY, Issue 1 2004J. R. Jauchem Summary 1 The role of histamine in heat-induced cardiovascular changes is uncertain. The purpose of this study was to examine effects of histamine H-1- and H-2-antagonism on heart rate, mean arterial blood pressure (MAP), localized body temperature changes, survival times, and lethal body temperatures that occur during the exposure of anaesthetized rats to 35 GHz radio frequency radiation (RFR). 2 Forty-eight ketamine-anaesthetized Sprague,Dawley rats were exposed, in several different treatment groups (n = 8 in each), to 35 GHz RFR at a level that resulted in significant body heating and subsequent death. During irradiation, a continuous increase in heart rate and a biphasic response in blood pressure (initial increase followed by a decrease) were observed in all groups of animals. 3 An H-1-antagonist, diphenhydramine (1 mg kg,1 body wt) and an H-2-antagonist, cimetidine (5 mg kg,1), administered after sustained RFR exposure, failed to reverse the RFR-induced hypotension. High doses of the drugs (5 and 10 mg kg,1, respectively) also did not alter the response. Post-RFR survival time was significantly decreased in the high-dose drug-treated group, compared with vehicle-treated (0.9% NaCl, 50% ethanol and 50% D5W) controls. 4 In experiments in which the two drugs were administered prior to RFR exposure, MAP in animals receiving high-dose antihistamines was significantly depressed compared with that of vehicle-treated animals during the first 35 min of RFR exposure. Antihistamine pretreatment, however, did not alter the total RFR exposure time required for death to occur. 5 In summary, pharmacological blockade of H-1 and H-2 receptors is not beneficial in anaesthetized rats made hypotensive by RFR exposure. This indicates that activation of H-1 and H-2 receptors by histamine does not occur to any significant extent and does not mediate the hypotensive response developed in this model of hyperthermia. [source] Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious ratsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2009W-S Vanessa Ho Background and purpose:, The cardiovascular effects of cannabinoids can be influenced by anaesthesia and can differ in chronic hypertension, but the extent to which they are influenced by acute hypertension in conscious animals has not been determined. Experimental approach:, We examined cardiovascular responses to intravenous administration of anandamide and the synthetic cannabinoid, (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone (WIN55212-2), in conscious male Wistar rats made acutely hypertensive by infusion of angiotensin II (AII) and arginine vasopressin (AVP). Rats were chronically instrumented for measurement of arterial blood pressure and vascular conductances in the renal, mesenteric and hindquarters beds. Key results:, Anandamide dose-dependently decreased the mean arterial blood pressure of rats made hypertensive by AII-AVP infusion, but not normotensive rats. Interestingly, acute hypertension also revealed a hypotensive response to WIN55212-2, which caused hypertension in normotensive animals. The enhanced depressor effects of the cannabinoids in acute hypertension were associated with increased vasodilatation in hindquarters, renal and mesenteric vascular beds. Treatment with URB597, which inhibits anandamide degradation by fatty acid amide hydrolase, potentiated the depressor and mesenteric vasodilator responses to anandamide. Furthermore, haemodynamic responses to WIN55212-2, but not to anandamide, were attenuated by the CB1 receptor antagonist, AM251 [N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2,4-dichlorophen yl)-4-methyl-1H-pyrazole-3-carboxamide]. Conclusions and implications:, These results broadly support the literature showing that the cardiovascular effects of cannabinoids can be exaggerated in hypertension, but highlight the involvement of non-CB1 receptor-mediated mechanisms in the actions of anandamide. [source] Cardio-respiratory reflexes evoked by phenylbiguanide in rats involve vagal afferents which are not sensitive to capsaicinACTA PHYSIOLOGICA, Issue 1 2010A. Dutta Abstract Aim:, Stimulation of pulmonary C fibre receptors by phenylbiguanide (PBG, 5-HT3 agonist) produces hypotension, bradycardia and tachypnoea or apnoea. However, tachypnoeic or apnoeic responses are not consistent. Therefore, this study was undertaken to delineate the actions of PBG on respiration and compared with those evoked by capsaicin (TRPV1 agonist). Methods:, Blood pressure, respiratory excursions and ECG were recorded in urethane anaesthetized adult rats. The effect of PBG or capsaicin was evaluated before and after ondansetron (5-HT3 antagonist), capsazepine (TRPV1 antagonist) or bilateral vagotomy. In addition, their effect on vagal afferent activity was also evaluated. Results:, Bolus injection of PBG produced concentration-dependent (0.1,100 ,g kg,1) hypotensive and bradycardiac responses, while there was tachypnoea at lower concentrations (0.1,3 ,g kg,1) and apnoea at higher concentrations (10,100 ,g kg,1). After vagotomy or after exposure to ondansetron both tachypnoeic and apnoeic responses were abolished along with cardiovascular responses. However, capsazepine (3 mg kg,1) did not block the PBG-induced reflex responses. Capsaicin (0.1,10 ,g kg,1), on the other hand, produced a concentration-dependent apnoea, hypotension and bradycardia but tachypnoea was not observed. Ondansetron failed to block the capsaicin-induced reflex response while bilateral vagotomy abolished bradycardiac and hypotensive responses and attenuated the apnoeic response. In another series, vagal afferent activity and cardio-respiratory changes evoked by PBG were blocked by ondansetron. However, capsaicin failed to activate the PBG-sensitive vagal afferents even though cardio-respiratory alterations were observed. Conclusions:, The present observations indicate that PBG produced tachypnoea at a lower concentration and apnoea at a higher concentration involving vagal afferents which are different from those excited by capsaicin. [source] Selective ,1 -adrenoreceptor blocking activity of newly synthesized acyl amino-substituted aryloxypropanolamine derivatives, DPJ 955 and DPJ 890, in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 4 2005K. Nandakumar The in-vivo ,-adrenoreceptor antagonistic activity of test compounds DPJ 955 and DPJ 890 was assessed against ,-adrenoreceptor agonist (isoprenaline) induced tachycardia in anaesthetized rats. The selectivity to block isoprenaline responses on different ,-adrenoreceptor subtypes (,1, ,2 and ,3) of the test compounds was carried out on isolated rat right atria, isolated rat uterus and isolated rat colon preparations, respectively. Intravenous injection of isoprenaline alone in anaesthetized rats caused hypotension and tachycardia. DPJ 955 or DPJ 890 alone produced a fall in mean arterial pressure and bradycardia in a dose-dependent manner. Administration of isoprenaline to anaesthetized rats pre-treated with test compounds significantly blocked both the tachycardial and hypotensive responses induced by isoprenaline. The test compounds shifted the concentration response curves of isoprenaline towards the right for isolated rat right atrial preparations, rat uterus and rat colon, indicating ,1, ,2 and ,3 adrenoreceptor blockade, respectively. The selectivity ratio for ,1/,-adrenoreceptors to DPJ 955 and DPJ 890 was 64.6 and 83.2, respectively. DPJ 890 was more potent in blocking ,1 -adrenoreceptors and was more selective towards ,1 receptors than to other ,-adrenoreceptor subtypes. In conclusion, DPJ 955 and DPJ890 have ,-adrenoreceptor blocking activity with high selectivity for the ,1 -adrenoreceptor subtype. [source] Direct Evidence for Imidazoline (I1) Receptor Modulation of Ethanol Action on Norepinephrine-Containing Neurons in the Rostral Ventrolateral Medulla in Conscious Spontaneously Hypertensive RatsALCOHOLISM, Issue 4 2007Guichu Li Background: Enhancement of the rostral ventrolateral medulla (RVLM) presympathetic (norepinephrine, NE) neuronal activity represents a neurochemical mechanism for the pressor effect of ethanol. In this study, we tested the hypothesis that ethanol action on RVLM presympathetic neurons is selectively influenced by the signaling of the local imidazoline (I1) receptor. To support a neuroanatomical and an I1 -signaling selectivity of ethanol, and to circumvent the confounding effects of anesthesia, the dose-related neurochemical and blood pressure effects of ethanol were investigated in the presence of selective pharmacological interventions that cause reduction in the activity of RVLM or nucleus tractus solitarius (NTS) NE neurons via local activation of the I1 or the ,2 -adrenergic receptor in conscious spontaneously hypertensive rats. Results: Local activation of the I1 receptor by rilmenidine (40 nmol) or by the I1/,2 receptor mixed agonist clonidine (1 nmol), and local activation of the ,2 -adrenergic receptor (,2AR) by the pure ,2AR agonist , -methylnorepinephrine (, -MNE, 10 nmol) caused reductions in RVLM NE, and blood pressure. Intra-RVLM ethanol (1, 5, or 10 ,g), microinjected at the nadir of the neurochemical and hypotensive responses, elicited dose-dependent increments in RVLM NE and blood pressure in the presence of local I1,but not ,2 -receptor activation. Only intra-NTS , -MNE, but not rilmenidine or clonidine, elicited reductions in local NE and blood pressure; ethanol failed to elicit any neurochemical or blood pressure responses in the presence of local activation of the ,2AR within the NTS. Conclusion: The findings support the neuroanatomical selectivity of ethanol, and support the hypothesis that the neurochemical (RVLM NE), and the subsequent cardiovascular, effects of ethanol are selectively modulated by I1 receptor signaling in the RVLM. [source] | ||||||||||