Tonic and phasic influences of nitric oxide on renal blood flow autoregulation in conscious dogs. (49/19128)

The aim of this study was to investigate the influence of the mean level and phasic modulation of NO on the dynamic autoregulation of renal blood flow (RBF). Transfer functions were calculated from spontaneous fluctuations of RBF and arterial pressure (AP) in conscious resting dogs for 2 h under control conditions, after NO synthase (NOS) inhibition [NG-nitro-L-arginine methyl ester hydrochloride (L-NAME)] and after L-NAME followed by a continuous infusion of an NO donor [S-nitroso-N-acetyl-DL-penicillamine (SNAP)]. After L-NAME (n = 7) AP was elevated, heart rate (HR) and RBF were reduced. The gain of the transfer function above 0.08 Hz was increased, compatible with enhanced resonance of the myogenic response. A peak of high gain around 0.03 Hz, reflecting oscillations of the tubuloglomerular feedback (TGF), was not affected. The gain below 0.01 Hz, was elevated, but still less than 0 dB, indicating diminished but not abolished autoregulation. After L-NAME and SNAP (n = 5), mean AP and RBF were not changed, but HR was slightly elevated. The gain above 0.08 Hz and the peak of high gain at 0.03 Hz were not affected. The gain below 0.01 Hz was elevated, but smaller than 0 dB. It is concluded that NO may help to prevent resonance of the myogenic response depending on the mean level of NO. The feedback oscillations of the TGF are not affected by NO. NO contributes to the autoregulation below 0.01 Hz due to phasic modulation independent of its mean level.  (+info)

Neurocardiac and cerebral responses evoked by esophageal vago-afferent stimulation in humans: effect of varying intensities. (50/19128)

OBJECTIVE: This study was designed to determine whether esophageal vago-afferent electrostimulation, over a wide range of stimulus intensities, can sustain a cardiac vago-efferent effect by way of central nervous system processing. METHODS: Studies were performed in ten healthy male subjects (23.9 +/- 6.3 years). Esophageal electrostimulation was carried out using a stimulating electrode placed in the distal esophagus. Stimulation of esophageal vago-afferent fibres was employed using electrical impulses (200 microseconds at 0.2 Hz x 128 s) varying from 2.7 to 20 mA. Respiratory frequencies, beat-to-beat heart rate autospectra and cerebral evoked potentials were recorded at baseline and at each stimulus intensity in random order. RESULTS: With esophageal electrical stimulation, we observed a small non-significant decrease in heart rate. There was a dramatic shift of the instantaneous heart rate power spectra towards enhanced cardiac vagal modulation with intensities as low as 5 mA. This effect was sustained throughout all intensities with no further change in either the low frequency or high frequency power. Conversely, there was a linear dose response relationship between cerebral evoked potential amplitude and stimulus intensity mainly occurring above perception threshold (10 mA). Esophageal stimulation had no significant effect on heart rate or respiratory frequency at any stimulus intensity. CONCLUSIONS: These results indicate that electrical stimulation of the distal esophagus across a wide range of current intensities elicits a reproducible shift in the heart rate power spectrum towards enhanced vagal modulation. The data suggest a closed loop afferent/efferent circuitry wherein tonic visceral afferent impulses appear to elicit a phasic or modulatory vago-efferent cardiac response in healthy subjects.  (+info)

Altered alpha 1-adrenoceptor subtypes mediated cardiac function after treatment of propranolol to rats. (51/19128)

AIM: To study inotropic and chronotropic effects mediated by alpha 1A- and alpha 1B-adrenoceptors after 5-d propranolol (Pro) treatment. METHODS: The positive inotropic and chronotropic effects mediated by alpha 1A and alpha 1B subtypes were determined on isolated left ventricular papillary muscles and right atrium in Pro- and NaCl-treated rats. RESULTS: The basic contractility of papillary muscles induced by phenylephrine (Phe) was 90 +/- 18 mg in Pro-treated rats and 53 +/- 17 mg in control group (P < 0.05). The increment on force of contraction was 20 +/- 12 mg in Pro-pretreated rats and 5 +/- 5 mg in NaCl-treated rats (P < 0.05). After preincubated with chloroethylclonidine, the increment on force of contraction was reduced in Pro-treated rats, but was not much changed in control group. Phe in presence of 5-methylurapidil induced positive inotropic effect with 13 +/- 5 mg in Pro-treated group, but not in NaCl-treated rats. Under the normal and the inhibited cardiac state, the maximal increment in beat rate mediated by alpha 1B showed no difference between the Pro-treated and NaCl-treated rats. CONCLUSION: After chronic treatment of Pro, alpha 1-adrenoceptor-mediated positive inotropic effect in rat heart was improved, which was mainly induced by stimulation of alpha 1B when beta-adrenoceptors were blocked.  (+info)

Pharmacokinetic-pharmacodynamic modeling of metoprolol stereoisomers in spontaneously hypertensive rat. (52/19128)

AIM: To study the combined pharmacokinetic-pharmacodynamic (PK-PD) model of metoprolol stereoisomers, and compare their inhibitory effects on cardiovascular system in the spontaneously hypertensive rats (SHR). METHODS: The drug concentration in plasma was measured by the reversed phase HPLC and the drug effects were recorded by polygraph. The pharmacokinetic parameters and the PK-PD model parameters were calculated. RESULTS: The plasma concentration-time profiles were adequately described by two-compartment model. Differences of Vd between (+)-Met and (-)-Met were found. The relationships between effects and concentration of effect compartment were represented by the sigmoid-Emax model. The Css50 of Vmax, dp/dtmax, and HR inhibitory effects of (+)-Met were larger than those of (-)-Met. CONCLUSION: Stereo-selective drug distribution and different potencies of the inhibitory effects of (+)-Met and (-)-Met existed in SHR.  (+info)

Histamine aggravated levothyroxine-induced cardiomyopathy in guinea pigs. (53/19128)

AIM: To study effects of histamine on cardiomyopathy. METHODS: Cardiomyopathy model was developed in guinea pig by i.p. levothyroxine 0.5 mg.kg-1.d-1 for 10 d. Langendroff's hearts were perfused. ECG and contractile force were recorded. Histamine (5 micrograms) was given by intra-aortic injection. Histamine content of coronary venous effluent was determined fluorometrically. RESULTS: Attack of histamine on cardiomyopathy was severer than that in normal hearts. Tachycardia was more prominent; atrioventricular conduction block occurred earlier; decrease in coronary flow was more marked. Uptakes of histamine were 37% in the model and 19% in the normal hearts (P < 0.01). CONCLUSION: Histamine aggravated levothyroxine-cardiomyopathy.  (+info)

Heart rate variability and ischaemia in patients with coronary heart disease and stable angina pectoris; influence of drug therapy and prognostic value. TIBBS Investigators Group. Total Ischemic Burden Bisoprolol Study. (54/19128)

AIMS: Determination of the influence of therapy with bisoprolol and nifedipine on the heart rate variability of patients from the Total Ischemic Burden Bisoprolol Study and examination of the prognostic value. METHODS AND RESULTS: Four hundred and twenty-two patients with stable angina were included. The heart rate variability was determined over a period of 24 h. Parameters determined: standard deviation of the mean of all corrected RR intervals, standard deviation of all 5 min mean cycle lengths, square root of the mean of the squared differences of successive corrected RR intervals. Nifedipine reduced the mean values of all heart rate variability parameters tested. Square root of the mean of the square differences of successive corrected RR intervals increased under bisoprolol. Standard deviation of the mean of all corrected RR intervals and standard deviation of all 5 min mean cycle lengths increased from low baseline values and declined from higher baseline values. The increase in heart rate variability under therapy was accompanied by a tendency towards a better prognosis. Patients with an increase in heart rate variability and simultaneous complete suppression of ischaemia under therapy displayed no serious events in the course of one year. CONCLUSIONS: The increase in the heart rate variability, which can be regarded as prognostically favourable, was predominantly observed under bisoprolol. The parameter constellation of an increase in heart rate variability and complete ischaemia suppression on the 48-h Holter ECG was associated with the greatest benefit.  (+info)

Effect of the cannabinoid receptor agonist WIN55212-2 on sympathetic cardiovascular regulation. (55/19128)

1. The aim of the present study was to analyse the cardiovascular actions of the synthetic CB1/CB2 cannabinoid receptor agonist WIN55212-2, and specifically to determine its sites of action on sympathetic cardiovascular regulation. 2. Pithed rabbits in which the sympathetic outflow was continuously stimulated electrically or which received a pressor infusion of noradrenaline were used to study peripheral prejunctional and direct vascular effects, respectively. For studying effects on brain stem cardiovascular regulatory centres, drugs were administered into the cisterna cerebellomedullaris in conscious rabbits. Overall cardiovascular effects of the cannabinoid were studied in conscious rabbits with intravenous drug administration. 3. In pithed rabbits in which the sympathetic outflow was continuously electrically stimulated, intravenous injection of WIN55212-2 (5, 50 and 500 microg kg(-1)) markedly reduced blood pressure, the spillover of noradrenaline into plasma and the plasma noradrenaline concentration, and these effects were antagonized by the CB1 cannabinoid receptor-selective antagonist SR141716A. The hypotensive and the sympathoinhibitory effect of WIN55212-2 was shared by CP55940, another mixed CB1/CB2 cannabinoid receptor agonist, but not by WIN55212-3, the enantiomer of WIN55212-2, which lacks affinity for cannabinoid binding sites. WIN55212-2 had no effect on vascular tone established by infusion of noradrenaline in pithed rabbits. 4. Intracisternal application of WIN55212-2 (0.1, 1 and 10 microg kg(-1)) in conscious rabbits increased blood pressure and the plasma noradrenaline concentration and elicited bradycardia; this latter effect was antagonized by atropine. 5. In conscious animals, intravenous injection of WIN55212-2 (5 and 50 microg kg(-1)) caused bradycardia, slight hypotension, no change in the plasma noradrenaline concentration, and an increase in renal sympathetic nerve firing. The highest dose of WIN55212-2 (500 microg kg(-1)) elicited hypotension and tachycardia, and sympathetic nerve activity and the plasma noradrenaline concentration declined. 6. The results obtained in pithed rabbits indicate that activation of CB1 cannabinoid receptors leads to marked peripheral prejunctional inhibition of noradrenaline release from postganglionic sympathetic axons. Intracisternal application of WIN55212-2 uncovered two effects on brain stem cardiovascular centres: sympathoexcitation and activation of cardiac vagal fibres. The highest dose of systemically administered WIN55212-2 produced central sympathoinhibition; the primary site of this action is not known.  (+info)

Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation. (56/19128)

1. The effects of intravenous administration of endothelin (ET) receptor antagonists SB-209670 (0.001-10.0 mg kg(-1)), SB-217242, SB-234551 (0.01-10.0 mg kg(-1)) and BQ-788 (0.001-1.0 mg kg(-1)) were investigated on trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the carotid vasculature of the anaesthetized cat. Comparisons were made with sumatriptan (0.003-3.0 mg kg(-1)) and alpha-CGRP8-37 (0.001-0.1 mg kg(-1)). 2. Trigeminal nerve ganglion stimulation produced frequency related increases in carotid blood flow, reductions in carotid vascular resistance and non-frequency related increases in blood pressure. Guanethidine (3 mg kg(-1), i.v.) blocked trigeminal nerve ganglion-induced increases in blood pressure but had no effect on changes in carotid flow or resistance. Maximal reductions in carotid vascular resistance was observed at 10 Hz, and this frequency was selected to investigate the effects of drugs on trigeminal nerve ganglion stimulation-induced responses in guanethidine treated cats. 3. Saline, alpha-CGRP8-37 SB-209670 and BQ-788 had little or no effect on resting haemodynamic parameters. SB-217242 (10 mg kg(-1), n=3) produced a 56% reduction in arterial blood pressure whereas SB-233451 (10 mg kg(-1), n=3) produced a 30% reduction in carotid vascular resistance. Sumatriptan produced dose-related reductions in resting carotid flow and increases (max. 104% at 0.3 mg kg(-1), n = 5) in vascular resistance. 4. SB-209670 (n=6-7), SB-217242 (n=3) and BQ-788 (n=3) produced inhibition of trigeminal nerve ganglion stimulation-induced reductions in carotid vascular resistance. Saline, SB-234551, alpha-CGRP8-37 and sumatriptan had no effect. 5. These data demonstrate ET(B) receptor blockade attenuates the vasodilator effects of trigeminal nerve ganglion stimulation in the carotid vascular bed of guanethidine pretreated anaesthetized cats.  (+info)