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1.
  • 1 The aims of the present study were to determine the cardiovascular effects of arachidonic acid (AA) and to investigate the peripheral mechanisms mediating these effects in haemorrhage‐induced hypotensive rats.
  • 2 Acute haemorrhage was induced by withdrawing a total volume of 2.2 mL blood/100 g bodyweight over a period of 10 min. Rats were then injected with 75–300 µg, i.c.v., AA and cardiovascular changes were monitored over the next 60 min. Plasma catecholamine and vasopressin levels, as well as plasma renin activity (PRA), were measured 10 min after injection of 150 µg AA in haemorrhage‐induced hypotensive awake rats. In addition, rats were pretreated with saline (1 mL/kg, i.v.), the vasopressin V1 receptor antagonist [β‐mercapto‐β,β‐cyclopentamethylenepropionyl1,O‐Me‐Tyr2,Arg8]‐vasopressin (10 µg/kg, i.v.), the α1‐adrenoceptor antagonist prazosin (500 µg/kg, i.v.), the non‐specific angiotensin II receptor antagonist saralasin (250 µg/kg, i.v.) or a combination of these three antagonists 5 min before injection of AA (150 µg, i.c.v.). The effects of these antagonists on responses to AA were determined.
  • 3 Arachidonic acid caused dose‐ and time‐dependent increases in mean arterial pressure and heart rate and reversed hypotension in haemorrhaged rats. Haemorrhage itself produced an increase in plasma catecholamine and vasopressin levels, as well as PRA; injection of AA produced further increases in these parameters, ranging from 39–123%, under hypotensive conditions. Under hypotensive conditions, pretreatment of rats with all three receptor antagonists produced similar partial blockade of the pressor response to AA, but not the increase in heart rate. Moreover, combined administration of all three receptor antagonists prior to the i.c.v. injection of 150 µg AA completely abolished the pressor response to AA in haemorrhage‐induced hypotensive rats.
  • 4 These results indicate that centrally administered AA reverses hypotension by increasing blood pressure and heart rate in the hypotensive setting. The observed increases in plasma catecholamine and vasopressin levels, as well as PRA, mediate the pressor response to AA in haemorrhage‐induced hypotensive rats.
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2.
  • 1 Published data concerning the effects of ovarian hormones on haemodynamic variability are contradictory. For the first time, the present study used radiotelemetric haemodynamic monitoring to investigate the long‐term effects of chronic oestrogen depletion and repletion on cardiovascular autonomic control and arterial baroreflex sensitivity (BRS) in female rats.
  • 2 Blood pressure (BP), heart rate (HR) and +dP/dtmax of arterial pressure (an estimate of myocardial contractility) were monitored in sham‐operated (SO), ovariectomized (OVX) and oestrogen‐replaced OVX rats (OVXE2) for 16 weeks. Cardiovascular autonomic control and baroreflexes were assessed by frequency domain analysis of interbeat intervals (IBI) and systolic BP (SBP).
  • 3 Compared with SO rats, OVX rats exhibited no changes in BP, short‐lived decreases in HR and sustained reductions in +dP/dtmax of arterial pressure. The high‐ (HF; 0.75–3 Hz) and low‐frequency (LF; 0.25–0.75 Hz) components of spectral power of IBI were significantly decreased and increased, respectively, by ovariectomy. An increase in the IBILF/HF ratio in OVX rats suggests a shift in the cardiac sympathovagal balance towards sympathetic dominance. Index α, the spectral index of spontaneous BRS, was reduced by OVX.
  • 4 Oestrogen replacement caused significant reductions in BP and HR and reversed OVX‐induced changes in +dP/dtmax of arterial pressure and cardiac autonomic activity. The LF oscillations of SBP were reduced in OVXE2 rats, suggesting a reduction in vascular sympathetic tone by oestrogen.
  • 5 These findings highlight the importance of long‐term oestrogen therapy in rectifying the detrimental effects of depletion of ovarian hormones on the cardiovascular system and baroreflex.
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3.
  • 1 Our aim was to identify mechanisms whereby prolonged fetal hypoxaemia alters renal function and urine production in fetal sheep.
  • 2 Fetal hypoxaemia was induced for 24 h by reducing uterine blood flow at 129.0±2.1 days of gestation (term 145–147 days), causing a reduction in fetal arterial O2 saturation (SaO2) from 52.5±2.3 to 22.0±1.3% (P<0.05). This hypoxaemia was initially associated with a mild acidaemia (pH 7.23±0.03).
  • 3 The glomerular filtration rate (GFR) increased from a control value of 1.8±0.03 mL/min per kg to a maximal value of 2.8±0.6mL/min per kg (P<0.05) at 4–5 h of hypoxaemia, returning to control levels by 6–9 h of hypoxaemia. After 4 h of hypoxaemia renal blood flow was no different to control values (144±8 mL/min per 100 g kidney weight) but after 24 h of hypoxaemia it had increased to 190±8 mL/min per 100 g kidney weight (P<0.05). Fractional reabsorption of Na+ in the proximal tubules decreased from a control value of 81.5±2.2 to 65.2±3.9% at 2–3 h of hypoxaemia (P<0.05) and remained reduced (68.5±3.1%) at the end of hypoxaemia (P<0.05). Fetal mean arterial pressure transiently increased (P<0.05) but returned to control values by 4–5 h of hypoxaemia. Fetal renal vascular resistance was not significantly altered during hypoxaemia. Fetal urine production increased from a control value of 12.3±2.1 mL/h per kg to a maximal value of 19.1±4.2 mL/h per kg at 4–5 h of hypoxaemia (P<0.05) and returned to control by 24 h of hypoxaemia.
  • 4 Our results indicate that prolonged fetal hypoxaemia leads to the inhibition of Na+ reabsorption in the proximal portion of the renal tubules. Changes in GFR induced by hypoxaemia were similar to those in fetal urine production and were not associated with changes in renal blood flow. We conclude that prolonged fetal hypoxaemia affects renal haemodynamics and the reabsorptive capacity of the renal tubules, resulting in a diuresis.
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4.
  • 1 Previous studies indicate that rutaecarpine blocks increases in blood pressure and inhibits vascular hypertrophy in experimentally hypertensive rats. The aim of the present study was to determine whether the effects of rutaecarpine are related to activation of prolylcarboxypeptidase (PRCP).
  • 2 Renovascular hypertensive rats (Goldblatt two‐kidney, one‐clip (2K1C)) were developed using male Sprague‐Dawley rats. Chronic treatment with rutaecarpine (10 or 40 mg/kg per day) or losartan (20 mg/kg per day) for 4 weeks to the hypertensive rats caused a sustained dose‐dependent attenuation of increases in blood pressure, increased lumen diameter and decreased media thickness, which was accompanied by a similar reduction in the media cross‐sectional area : lumen area ratio in mesenteric arteries compared with untreated hypertensive rats.
  • 3 Angiotensin (Ang) II expression was significantly increased in mesenteric arteries of hypertensive rats compared with sham‐operated rats. No significant differences in plasma AngII levels were observed between untreated hypertensive and sham‐operated rats. Hypertensive rats treated with high‐dose rutaecarpine had significantly decreased Ang II levels in both the plasma and mesenteric arteries.
  • 4 Expression of PRCP protein or kallikrein mRNA was significantly inhibited in the right kidneys and mesenteric arteries of hypertensive rats. However, expression of PRCP protein and kallikrein mRNA was significantly increased after treatment with rutaecarpine or losartan (20 mg/kg per day).
  • 5 The data suggest that the repression of increases in systolic blood pressure and reversal of mesenteric artery remodelling by rutaecarpine may be related to increased expression of PRCP in the circulation and small arteries in 2K1C hypertensive rats.
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5.
  • 1 Several groups have reported that melatonin produces a significant decrease in blood pressure in mammals and that pinealectomy in rats causes hypertension. The purpose of the present study was to investigate the effects of melatonin and bicuculline methiodide on the blood pressure of rats, both in the developing and fully developed stage of stress‐induced hypertension (SIH).
  • 2 Rats with SIH were generated by mild electric foot shocks for 15 days, after which tail arterial systolic pressure and plasma angiotensin (Ang) II levels were measured. The effects of melatonin injections (i.p. or i.c.v.) on mean arterial pressure (MAP) in rats with SIH were also determined.
  • 3 Pretreatment with 1 mg/kg, i.p., melatonin significantly diminished the elevated tail arterial systolic pressure and plasma AngII levels caused by 15 days stress. The suppressive effects of melatonin were blocked by i.p. injection of 1 mg/kg bicuculline methiodide, an antagonist of the GABAA receptor.
  • 4 Intraperitoneal (0.2, 0.5 and 1 mg/kg) or i.c.v. (0.15 and 1.5 µg/3 µL) injection of melatonin produced a dose‐dependent lowering of MAP in rats with SIH. The antihypertensive response induced by melatonin was blocked by injection of both 1 mg/kg, i.p., and 1.5 × 106 µg/3 µL, i.c.v., bicuculline methiodide.
  • 5 In conclusion, melatonin not only prevents increases in blood pressure during the developing stage of SIH, but can also reduce the blood pressure of rats that have already developed SIH. The antihypertensive effect of melatonin may be mediated by GABAA receptors through inhibition of plasma AngII levels.
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6.
  • 1 Low doses (0.1–1.0 mg/kg) of the converting enzyme inhibitor captopril given intravenously to pithed rats were followed by long lasting falls in systolic and diastolic arterial blood pressures. Concomit-antly pressor responses were reduced to either electrical stimulation of the thoraco-lumbar sympathetic outflow or intravenous injection of the ganglion stimulant McNeil-A-343. Positive chronotropic responses of the heart to cardiac nerve stimulation were unchanged after relatively large doses of the drug (3.0 mg/kg).
  • 2 The reductions in arterial blood pressure and pressor responses to McNeil-A-343 caused by captopril persisted following β-adrenoreceptor blockade, renal sympathectomy or unilateral nephrectomy, but did not occur after acute bilateral nephrectomy nor during sodium and water retention due to unilateral nephrectomy plus subacute administration of desoxycorticosterone and saline.
  • 3 Pressor responses to noradrenaline were reduced after 1.0 mg/kg captopril i.v. whereas those to methoxamine or vasopressin were unaltered after 5.0 mg/kg.
  • 4 It is concluded that in the rat, after elimination of sympathetic tone by pithing, the level of the arterial blood pressure and the magnitude of pressor responses to peripheral sympathetic nerve activation depend on the basal activity of the renin-angiotensin system. This maintains sufficient angiotensin II production to ensure retention of some tone in resistance vessels together with presynaptic augmentation of noradrenaline output at a sympathetic postganglionic nerve endings. The latter effects are abolished after converting enzyme inhibition with captopril, consequent to reduced tissue levels of angiotensin II and perhaps potentiation of the actions of bradykinin.
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7.
  • 1 The reflex effects of intravenous phenylephrine, sodium nitroprusside or acute haemorrhage in rabbits were examined as indices of baroreceptor reflex function.
  • 2 The slope of the linear regression of heart period: mean arterial pressure relationship was significantly greater (P<0.01) when buffering the pressor stimulus than either depressor stress.
  • 3 Captopril (1 mg/kg i.v.) had no effect on the slope of the relationship to either pressor or depressor stimuli.
  • 4 The clinical and experimental observation of hypotension without bradycardia after captopril could not be confirmed in the present study to be a result of changes in baroreflex sensitivity.
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8.
  • 1 The pathogenesis of acute renal failure (ARF) in sepsis is multifactorial. The role of nitric oxide (NO) in septic ARF has been a source of controversy. We hypothesized that endotoxaemia‐induced exacerbation of inducible nitric oxide synthase (iNOS)‐related NO release impairs renal oxygenation and contributes to ARF in anaesthetized rats.
  • 2 In the present study, rats received lipopolysaccharide (2.5 mg/kg) for 30 min. Two hours later, fluid resuscitation was started (HES130; 5 mL/kg per h after a 5 mL/kg bolus) supplemented either by the NO donor nitroglycerin (NTG; 0.5 µg/kg per min after a 2 µg/kg bolus), the selective iNOS inhibitor 1400W (3 mg/kg per h after a 3 mg/kg bolus) or both. Systemic haemodynamics and renal microvascular Po 2Po 2) were recorded continuously. Furthermore, creatinine clearance, plasma NOx (nitrate + nitrite + S‐nitrosothiols) levels and the expression of iNOS mRNA were measured.
  • 3 Endotoxaemia reduced renal blood flow, decreased mean arterial pressure, resulted in anuria and was associated with an increase in plasma NOx levels and renal iNOS expression. Renal µPo 2 deteriorated gradually during endotoxaemia and there was a significant decrease in renal O2 delivery and consumption. Manipulation of NO levels had no beneficial effect on systemic haemodynamics, renal µPo 2 or creatinine clearance over standard fluid resuscitation. The application of 1400W+NTG significantly reduced plasma NOx levels compared with fluid resuscitation and NTG alone.
  • 4 Neither iNOS inhibition, NO donation nor a combination of both showed beneficial effects on systemic haemodynamics, renal oxygenation and renal function compared with fluid resuscitation alone. Our results question the proposed key role of NO in the pathogenesis of septic ARF in rats.
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9.
10.
11.
Effects of dipeptidyl peptidase iv inhibition on arterial blood pressure   总被引:1,自引:0,他引:1  
  • 1 The aim of the present study was to determine whether inhibition of dipeptidyl peptidase IV (DPP IV) elevates arterial blood pressure and whether any such effect is dependent on genetic background, the sympathetic nervous system and Y1 receptors. The rationale behind this study was that: (i) neuropeptide (NP) Y1–36 and peptide YY1–36 (PYY1–36) are endogenous Y1 receptor agonists and are metabolised by DPP IV to NPY3–36 and PYY3–36, which are not Y1 but rather selective Y2 receptor agonists; (ii) Y1 receptors mediate vasoconstriction, whereas Y2 receptors have little effect on vascular tone; (iii) vaso‐constrictor effect of the Y1 receptor is enhanced in spontaneously hypertensive rats (SHR) compared with normotenisve Wistar‐Kyoto (WKY) rats; and (iv) NPY1–36 is released from sympathetic nerve terminals.
  • 2 We examined the effects of acute administration of 3‐N‐[(2S,3S)‐2‐amino‐3‐methylpentanoyl]‐1,3‐thiazolidine (P32/98; a DPP IV inhibitor) on arterial blood pressure in anaesthetized adult SHR and WKY rats in the absence and presence of either captopril, hydralazine or chlorisondamine to lower basal mean arterial blood pressure (MABP) by different mechanisms (inhibition of angiotensin‐converting enzyme, direct vasodilation and ganglionic blockade, respectively).
  • 3 In naïve SHR with severely elevated basal blood pressures (MABP = 176 ± 3 mmHg; n = 4), i.v. boluses (1, 3 and 10 mg/kg) of P32/98 did not affect blood pressure.
  • 4 When basal blood pressure was reduced by pretreatment of SHR with either captopril (30 mg/kg, i.v.; MABP = 116 ± 3 mmHg; n = 9) or hydralazine (5 mg/kg, i.p.; MABP = 84 ± 3 mmHg; n = 7), P32/98 (1, 3 and 10 mg/kg) caused significant dose‐related increases in arterial blood pressure (4 ± 2, 10 ± 2 and 12 ± 3 mmHg in the captopril‐pretreated group, respectively (P < 0.01); 5 ± 2, 8 ± 3 and 11 ± 4 mmHg in the hydralazine‐pretreated group, respectively (P < 0.01)).
  • 5 The increases in arterial blood pressure induced by P32/98 in captopril‐ or hydralazine‐pretreated SHR were entirely blocked by pretreatment with the selective Y1 receptor antagonist N2‐(diphenylacetyl)‐N‐[(4‐hydroxyphenyl)methyl]‐d ‐arginine amide (BIBP 3226; 6 mg/kg per h).
  • 6 When basal blood pressure was reduced in SHR by pretreatment with chlorisondamine (10 mg/kg, s.c.; MABP = 108 ± 4 mmHg; n = 7), inhibition of DPP IV with P32/98 did not affect arterial blood pressure. Basal heart rate in chlorisondamine‐treated SHR was significantly reduced compared with naïve SHR, captopril‐pretreated SHR and hydralazine‐pretreated SHR, indicating effectiveness of ganglionic blockade.
  • 7 Unlike the results in genetically hypertensive animals, in normotensive WKY rats pretreated with captopril (30 mg/kg, i.v.; MABP = 81 ± 4 mmHg; n = 6), or hydralazine (5 mg/kg, i.p.; MABP = 63 ± 4 mmHg; n = 4) or chlorisondamine (10 mg/kg, s.c.; MABP = 63 ± 4 mmHg; n = 5), P32/98 did not affect arterial blood pressure.
  • 8 We conclude that, in genetically susceptible animals, inhibition of DPP IV increases arterial blood pressure via Y1 receptors when elevated blood pressure is reduced with antihypertensive drugs provided that the sympathetic nervous system is functional. The results suggest vigilance because DPP IV inhibitors are used more widely in hypertensive patients treated with antihypertensive drugs.
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12.
  • 1 It has been shown that inhaled isoflurane limits the size of myocardial infarcts. The aim of the present study was to examine the effects of emulsified isoflurane on cardiac function and myocardial apoptosis in an ischaemia model of myocardial injury.
  • 2 In the first study, 48 rats were randomly allocated to six groups (n = 8 in each): control (saline); emulsified isoflurane (EIso) at 1, 2 or 4 mL/kg; 30% intralipid (vehicle for EIso); and sham operated. Rats received isovolumetric intravenous infusions for 30 min and then, 30 min after cessation of the infusion, 90 min coronary occlusion. Haemodynamics and myocardial infarct size were measured. In the second study, another 48 rats were randomized into six groups (n = 8 in each). After 90 min ischaemia, rats were killed for histopathological study, immunohistochemical evaluation and apoptosis measurement.
  • 3 Pretreatment with 2 and 4 mL/kg EIso significantly attenuated decreases in left ventricular systolic pressure and dP/dtmax, and increases in left ventricular end‐diastolic pressure and –dP/dpmax, and alleviated myocardial injury compared with the control, intralipid and 1 mL/kg EIso groups (P < 0.05). Infusion of 1 mL/kg EIso and intralipid had no effect on haemodynamics, infarct size or histological variables.
  • 4 Expression of Bcl‐2 was increased, whereas expression of Bax and caspase 3 was decreased, after preconditioning with 2 and 4 mL/kg EIso (P < 0.05). The apoptotic index in the 2 and 4 mL/kg Eiso‐treated groups was reduced compared with that in the control and intralipid groups (P < 0.01).
  • 5 In conclusion, EIso ameliorates cardiac dysfunction, attenuates myocardial damage and inhibits apoptosis after ischaemia, which may be attributed, in part, to diminished expression of apoptosis‐related protein.
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13.
  • 1 In the present study, we investigated the effects of inhibition of the lateral hypothalamus (LH) neurotransmission with bilateral microinjection of CoCl2, a non‐selective blocker of neurotransmission, on modulation of cardiac baroreflex responses in conscious rats as well as the involvement of LH glutamatergic neurotransmission in this modulation.
  • 2 Reflex bradycardiac and tachycardiac responses to blood pressure increases (following i.v. infusion of phenylephrine) or decreases (following i.v. infusion of sodium nitroprusside) were investigated in conscious male Wistar rats. Responses were evaluated before and after microinjection of 1 nmol/100 nL CoCl2, 2 nmol/100 nL 1,2,3,4‐tetrahydro‐6‐nitro‐2,3‐dioxobenzoquinoxaline‐7‐sulphonamide (NBQX; a selective non‐N‐methyl‐d ‐aspartate (NMDA) glutamate receptor antagonist) or different doses (2, 4 or 8 nmol/100 nL) of the selective NMDA glutamate receptor antagonist LY235959.
  • 3 Microinjection of CoCl2 into the LH had no effect on the tachycardiac baroreflex response, but did evoke a decrease in the reflex bradycardia caused by increases in blood pressure. Microinjection of NBQX into the LH had a similar effect on reflex bradycardia as CoCl2, but had no effect on the tachycardiac response. Microinjection of increasing doses of LY235959 into the LH had no effect on the cardiac baroreflex response.
  • 4 In conclusion, the data suggest that the LH has a tonic facilitatory influence on the parasympathetic component of the baroreflex. The results also indicate that this facilitatory influence is mediated by local LH glutamatergic neurotransmission through non‐NMDA glutamatergic receptors.
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14.
15.
In the present study, we investigated the effects induced by fluoxetine treatment (10 mg/kg) for either 1 or 21 consecutive days on arterial pressure and heart rate basal levels, baroreflex activity, hemodynamic responses to vasoactive agents and cardiovascular responses to acute restraint stress. Mild hypertension was observed after 21 days of treatment, but not after administration for 1 day. Moreover, chronic treatment affected the baroreflex control of heart rate, which was characterized by a reduced reflex tachycardia and an enhanced bradycardiac baroreflex response. The pressor responses to systemic administration of the selective α(1)-adrenoceptor agonist phenylephrine, as well as the depressor responses to systemic infusion of the nitric oxide donor sodium nitroprusside, were reduced after chronic fluoxetine treatment. Fluoxetine treatment for 21 days reduced both the pressor and tachycardiac responses evoked by acute restraint stress. In conclusion, the results indicate the development of mild hypertension after chronic fluoxetine treatment. This effect was followed by changes in the baroreflex control of heart rate and altered vascular responsiveness to pressor and depressor agents, which may explain, at least in part, the increase in arterial pressure. Chronic fluoxetine treatment also affected cardiovascular responses to restraint stress, thus indicating that fluoxetine may affect cardiovascular adaptation under conditions of stress.  相似文献   

16.
  • 1 Suppressing apoptosis and downregulating K+ channels in pulmonary artery smooth muscle cells (PASMC) have been implicated in the development of pulmonary vascular medial hypertrophy and pulmonary arterial hypertension (PAH). Previous studies have shown that selective serotonin re‐uptake inhibitors (SSRIs) protected against PAH. The aim of the present study was to investigate the involvement of Kv1.5 channels and apoptosis in the protective effect of the SSRI fluoxetine against PAH.
  • 2 Monocrotaline (MCT) was used to establish PAH in Wistar rats. Fluoxetine (2 and 10 mg/kg per day) was administered by gavage once a day for 3 weeks. Three weeks after the induction of PAH by MCT, pulmonary haemodynamic measurements and pulmonary artery morphological assessments were undertaken, along with detection of apoptosis and Kv1.5.
  • 3 Fluoxetine (2 and 10 mg/kg per day) decreased pulmonary artery pressure, reduced the right ventricular index and inhibited the increase in medial wall thickness of pulmonary arteries in established PAH. Fluoxetine (10 mg/kg per day) reduced the expression of Bcl‐2 and Bcl‐xL protein, increased the expression of cleaved caspase 3 protein and enhanced the expression of Kv1.5 protein and mRNA in pulmonary arteries. Furthermore, fluoxetine (10 mg/kg per day) significantly suppressed proliferation and enhanced apoptosis of PASMC in MCT‐induced PAH.
  • 4 In conclusion, fluoxetine protects against MCT‐induced PAH by suppressing PASMC proliferation, inducing PASMC apoptosis and upregulating Kv1.5 channels.
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17.
Heart failure (HF) is characterized by activation of both neurohumoral and sympathetic nervous systems. Specifically, HF is associated with increases in vasopressin (VP) and endothelin (ET) and in arterial baroreflex dysfunction. Hypothesis was that central ET-1 potentiates VP secretion in HF due to impaired pressor response and diminished arterial baroreflex inhibition. Male Sprague-Dawley rats were studied 42 to 54 days after sham or coronary ligation (HF) and 7 days after sinoaortic denervation (SAD). Conscious rats received intracerebroventricular artificial cerebrospinal fluid (CSF), 10 pmol of ET-1, 40 nmol BQ123, or both. Basal mean arterial pressure (MAP) did not differ, but heart rate and left ventricular end-diastolic pressure were significantly higher in HF and HF/SAD. Baseline VP was higher in both HF and HF/SAD: 5.9 +/- 0.4 pg/ml and 5.6 +/- 0.7 pg/ml versus sham 2.8 +/- 0.2 and sham-SAD 1.6 +/- 0.2 (p < 0.001). ET-1 increased MAP in sham rats by 16.0 +/- 1.4 mm Hg, but only by 7.4 +/- 2.2 mm Hg in HF (p < 0.05 versus sham) and 5.8 +/- 2.4 mm Hg in HF/SAD (p < 0.01 versus sham SAD). Tachycardic response was attenuated in HF/SAD compared with HF alone. After ET-1, VP increased by 3.3 +/- 2.7 pg/ml in sham and 13.3 +/- 2.6 pg/ml in HF (p < 0.05), but only by 2.3 +/- 0.7 pg/ml in HF/SAD (p < 0.01 versus HF). BQ123 blocked all responses to exogenous ET-1 but had no effect on baseline values. Thus, ET-evoked a lower pressor response in HF due to an impaired ability to increase heart rate and cardiac output. ET-1-induced VP release in HF was higher than in controls as a result of lower pressor response or impaired arterial baroreflex. In contrast to rats with normal left ventricular function, sinoaortic denervation in HF failed to potentiate either pressor response or VP secretion. These findings suggest that acute, though modest, increases in afterload may increase left atrial pressure more in HF/SAD such that cardiopulmonary reflexes may be activated or natriuretic peptides may be released that further restrain both pressor and VP responses.  相似文献   

18.
《General pharmacology》1996,27(2):299-304
  • 1.1. It is well known that α1A-adrenoceptors have binding sites for imidazolic and for phenylethylaminic drugs. A study was made relating α1A-adrenoceptor involvement in cardiovascular responses to intracerebroventricular (ICV) injection of BHT-920, an imidazoliclike drug, and phenylephrine, a phenylethylaminic drug, in conscious sham-operated and sinoaortically-denervated rats.
  • 2.2. In sham-operated rats, cardiovascular responses to BHT-920 (30 μg, ICV) were increase of blood pressure and bradycardia but in sinoaortically denervated rats, after the pressor response, a decrease of blood pressure was also seen. The pressor and bradycardic responses to agonist were greater in sinoaortically denervated rats than in sham-operated rats. Phenylephrine (90 μg, ICV) showed a biphasic effect on blood pressure: an increase followed by a decrease, and bradycardia. The cardiovascular responses to phenylephrine in sinoaortic-denervated rats were greater than in sham-operated rats.
  • 3.3. In sinoaortically denervated and sham-operated rats subchronically treated with the α1-adrenoceptor antagonist prazosin (0.5 mg kg−1, intraperitoneally twice daily, for 6 days), an increase of cardiovascular responses to ICV administration of BHT-920 and phenylephrine was seen.
  • 4.4. Baroreceptor deafferentation by sinoaortic denervation enhances the cardiovascular responses to BHT-920 and phenylephrine. The effects of BHT-920 could be mediated by brain α1A-adrenoceptors because this agonist has an imidazoliclike structure; phenylephrine could also be activating central α1A-adrenoceptors. The enhanced cardiovascular responses after prazosin treatment could also be due to a supersensitivity of brain α1A-adrenoceptors.
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19.
  • 1 The actions of intravenously administered 5-hydroxytryptamine (5-HT) have been analysed in conscious DOCA-salt hypertensive rats using selective 5-HT receptor agonists and antagonists to determine the receptor mechanisms involved and to compare them with those in conscious normotensive rats.
  • 2 In both normotensive and hypertensive rats 5-HT, 3 and 10 μg i.v., produced a complex triphasic effect on blood pressure consisting of an initial short lasting depressor response, which was followed by a pressor response and then, finally, a hypotensive phase. Marked decreases in heart rate were observed immediately after dosing, which were followed by small increases in rate.
  • 3 The selective 5-HT3-receptor agonist, 2-methyl 5-HT, 3–30 μg i.v., produced immediate and marked dose-related decreases in blood pressure and heart rate in both normotensive and DOCA-salt hypertensive rats. The 5-HT3-receptor antagonist, MDL 72222, 0.03 and 0.1 mg/kg i.v., antagonised these effects in both normotensive and DOCA-salt hypertensive rats. Treatment with MDL 72222, 0.3 mg/kg i.v., abolished the initial depressor response and bradycardia produced by 5-HT.
  • 4 The 5-HT2 receptor agonist, α-methyl 5-HT, 3–30 μg i.v., produced dose-related increases in blood pressure which were significantly greater in magnitude in DOCA-salt hypertensive than normotensive rats. Bradycardia was observed consistently at 30 μg only. The 5-HT2 receptor antagonist, ketanserin, 0.03-0.3 mg/kg i.v., caused a dose-dependent antagonism of the pressor responses produced by α-methyl 5-HT, but had no effect on the increases in blood pressure produced by angiotensin. Ketanserin also antagonised the pressor responses produced by 5-HT in rats pretreated with MDL 72222.
  • 5 5-Carboxamidotryptamine (5-CT), the selective ‘5-HT1-like’ receptor agonist, at doses of 0.1–3 μg i.v. produced dose-related decreases in blood pressure which were more pronounced in the DOCA-salt hypertensive rats than in normotensive rats. These depressor responses were dose-dependently antagonised by methiothepin, 0.3 and 1 mg/kg, i.v. which did not antagonise the depressor responses produced by isoprenaline 0.1 μg/kg i.v. In rats pretreated with MDL 72222 and ketanserin, 5-HT produced dose-related depressor responses which were also antagonised by methiothepin 1 mg/kg i.v. and presumably mediated by 5-HT1-like receptors.
  • 6 In this study, selective 5-HT receptor agonists and antagonists have been used to mimic and block, respectively, the various phases of the 5-HT response. It is concluded that in the conscious rat, the complex cardiovascular effects of 5-HT involve stimulation of at least three different 5-HT receptors (for nomenclature see Bradley, Engel, Feniuk, Fozard, Humphrey, Middlemiss, Mylecharane, Richardson & Saxena, 1986). The initial depressor response and bradycardia involves activation of 5-HT3-receptors, the secondary vasopressor effect, which is significandy greater in DOCA-salt than normotensive rats results from stimulation of 5-HT2 receptors and the late vasodepressor response is due to vasodilatation via ‘5-HT1-like’ receptors.
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20.
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