Fall In Arterial Blood Pressure Research Articles

Serotonergic neurons of the caudal raphe nuclei activated in response to hemorrhage in the rat

The response to a sudden, severe loss of blood volume is complex and results in a drastic fall in arterial blood pressure and sympathoinhibition. The present study examines the distribution of serotonergic neurons in the caudal raphe involved in the mediation of the response to severe hemorrhage. Hemorrhage was performed in rats anesthetised with urethane by withdrawal of blood at a rate of 1 ml/min for approximately 4 min until blood pressure fell to 50 mm Hg. Sections through the brainstem were processed immunohistochemically to identify Fos, the protein product of the proto-oncogene c- fos expressed in the nucleus of neurons activated during the hemorrhage stimulus, and double-labeled to identify serotonin (5-hydroxytryptamine; 5-HT) content of cells. In response to hemorrhage, double-labeled Fos/5-HT neurons were located in the B3 region which includes the raphe magnus (RM) and its lateral extension. Hemorrhage-induced Fos-positive neurons that were not serotonergic were located in raphe pallidus (RP), parapyramidal cell group (PP), and the B3 region. Serotonergic neurons not activated by hemorrhage were located in the nucleus raphe pallidus, the parapyramidal cell group, the raphe obscurus (RO), and the B3 region. The specific rostrocaudal distribution of activated neurons may indicate different functions of groups of neurons in the response to hemorrhage.

Utility of transesophageal atrial pacing in the diagnostic evaluation of patients with unexplained syncope associated or not with palpitations

Background: Noninvasive studies are often negative in patients with syncope, normal surface ECG and without heart disease. The purpose of the study was to determine the diagnostic impact of an esophageal electrophysiological study performed during a consultation. Methods: A total of 154 patients aged from 16 to 87 years were consecutively recruited for unexplained syncope; they had a normal ECG in sinus rhythm, no documented arrhythmia and no patent heart disease. Half of them complained of palpitations. Electrophysiologic study was performed during a consultation by transesophageal route: rate of 2nd d AV block occurrence during atrial pacing and sinus node recovery time were determined; programmed atrial stimulation using one and two atrial extrastimuli were delivered in control state and then after infusion of 0.02–1 μg/min of isoproterenol; arterial blood pressure was monitored. Results: (1) Electrophysiologic study was positive in 107 patients (69%); (2) sinus node dysfunction was noted in 9 patients (6%); (3) atrioventricular conduction disturbances were noted in 2 patients (1%); (4) vasovagal reaction which associated a junctional bradycardia and a fall of arterial blood pressure and which reproduced spontaneous symptoms was provoked by isoproterenol infusion in 21 patients (14%); (5) sustained atrial fibrillation was induced in 23 patients (15%); and (6) paroxysmal junctional tachycardia was induced in 52 patients (34%). Patients with negative study were younger (44±21.5 years) than those with sinus node dysfunction or atrial fibrillation (71±9 and 63±14 years, respectively). The treatment was guided by these data: patients with inducible atrial fibrillation were treated by antiarrhythmic drugs and those with inducible paroxysmal junctional tachycardia by the radiofrequency ablation of reentrant circuit. Syncope disappeared in all patients but 2. Conclusion: Esophageal electrophysiologic study performed during a consultation was a safe, rapid and economic means to detect an arrhythmia (sinus node dysfunction or supraventricular tachycardia) in patients with dizziness/syncope and palpitations in half cases. Supraventricular tachycardia was clearly an underestimated cause of syncope in this population.

Body sodium and volume homeostasis.

maintenance of a “milieu interieur,” which allows our cells to function away from the ancient sea, is one of the most important functions of the body. Maintenance of constant extracellular osmolarity and sodium concentration depends on a precise balance between intake and excretion of sodium and

Clinical Features of CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks, strokes, and vascular dementia. Various mutations in the Notch3 gene cause the disease, whereas the mechanism of how they cause the disorder remains unknown. We recently identified two Japanese CADASIL families with an R141C mutation. The mean age of onset was 44.6, and the main symptoms were recurrent strokes and progressive motor disturbances in extremities, as well as pseudobulbar palsy. Besides those in white matter and basal ganglia, ischemic lesions in temporal edge and corpus callosum were present on magnetic resonance images, which seemed to be characteristic of CADASIL. Moreover, in our cases, nocturnal arterial blood pressure fall was significantly lower in patients compared with control subjects, suggesting that it might be partly associated with ischemic lesions in deep white matter in CADASIL. We also compared Japanese and Caucasian CADASIL cases and found that dementia and pseudobulbar palsy were observed more frequently in Japanese patients, although typical migraine was rather rare. In the present study, we describe the clinical features of CADASIL, hoping to help reveal the mechanism of chronic ischemic brain diseases, including leukoaraiosis or Binswanger's disease.

Complex regional haemodynamic effects of anandamide in conscious rats.

1. Experiments were carried out in conscious, chronically instrumented, male, Sprague-Dawley rats to delineate the regional haemodynamic effects of the putative endogenous cannabinoid, anandamide, (0.075 - 3 mg kg(-1)), and to dissect some of the mechanisms involved. 2. At all doses of anandamide, there was a significant, short-lived increase in mean arterial blood pressure associated with vasoconstriction in renal, mesenteric and hindquarters vascular beds. 3. The higher doses (2.5 and 3 mg kg(-1)), caused an initial, marked bradycardia accompanied, in some animals, by a fall in arterial blood pressure which preceded the hypertension. In addition, after the higher doses of anandamide, the hindquarters vasoconstriction was followed by vasodilatation. 4. Although some of the effects described above resembled those of 5-HT (25 microg kg(-1)), the bradycardia and hypotensive actions of the latter were abolished by the 5HT(3)-receptor antagonist, azasetron, whereas those of anandamide were generally unaffected. 5. None of the cardiovascular actions of anandamide were influenced by the CB(1)-receptor antagonist, AM 251, but its bradycardic effect was sensitive to atropine, and its hindquarters vasodilator action was suppressed by the beta(2)-adrenoceptor antagonist, ICI 118551. 6. The results differ, in several aspects, from those previously reported in anaesthetized animals, and underscore the important impact anaesthesia can have on responses to anandamide.

Renal sympathoinhibition mediated by 5-HT(1A) receptors in the RVLM during severe hemorrhage in rats.

The role of 5-hydroxytryptamine type 1A (5-HT(1A)) receptors in the rostral ventrolateral medulla (RVLM) in the mediation of the sympathoinhibitory and hypotensive responses to severe hemorrhage was examined in pentobarbital sodium-anesthetized rats. The control response to hemorrhage (1 ml/min to 50 mmHg) consisted of a fall in arterial blood pressure and an initial baroreflex increase in renal sympathetic nerve activity followed after 2 min by a rapid decline in blood pressure accompanied by a decrease in renal sympathetic nerve activity. In response to hemorrhage in animals in which the specific 5-HT(1A) receptor antagonist WAY-100635 was microinjected into the pressor area of the RVLM, the fall in blood pressure was delayed and attenuated while renal sympathetic nerve activity was increased and maintained above baseline. In barodenervated animals with blockade of RVLM 5-HT(1A) receptors, there was no change in renal sympathetic nerve activity in response to hemorrhage. These data suggest that renal sympathoinhibition elicited in response to severe hemorrhage is mediated by 5-HT(1A) receptors in the RVLM.

The role of alpha(1)-adrenoceptors and 5-HT(1A) receptors in the control of the micturition reflex in male anaesthetized rats.

1. The effects of the alpha(1)-adrenoceptor antagonists doxazosin (0.1 -- 2 mg kg(-1)), RS-100329 (alpha(1A); 0.01 -- 1 mg kg(-1)), RS-513815 (Ro 151-3815, alpha(1B); 0.3 -- 3 mg kg(-1)) and BMY 7378 (alpha(1D); 0.1 -- 1 mg kg(-1)), the 5-HT(1A) receptor agonist, 8-OH-DPAT (0.03 -- 0.3 mg kg(-1)) and antagonist WAY-100635 (0.03 -- 0.3 mg kg(-1)) were investigated (i.v.) on the 'micturition reflex' in the urethane anaesthetized male rat. 2. Reflex-evoked urethra contractions were most sensitive to the inhibitory action of RS-100329, followed by doxazosin, BMY 7378 and WAY-100635 and then RS-513815. The maximum inhibition was 66, 63, 54, 46 and 22% at doses of 0.3, 0.5, 0.3, 0.3 and 3 mg kg(-1) respectively. 3. BMY 7378 and 8-OH-DPAT decreased, while WAY-100635 increased, the pressure threshold to induce bladder contraction. WAY-100635 (0.01 mg kg(-1)) blocked the effects of BMY 7378 (1 mg kg(-1)) on bladder pressure and volume threshold. 4. Doxazosin, RS-100329 and BMY 7378 had a similar potency in inducing a fall in arterial blood pressure while WAY-100635 only caused a fall at the highest dose. 5. Therefore, reflex-evoked urethral contraction involves the activation of alpha(1A/1D)-adrenoceptors, as BMY 7378 and RS-100329 are similarly potent in attenuating this effect. The ability of WAY-100635 to attenuate this contraction may suggest that 5-HT(1A) receptors are also involved. However, as this inhibition occurred at the highest dose of WAY-100635, which also caused a fall in arterial blood pressure; this effect is considered to be due to blockade of alpha(1)-adrenoceptors not 5-HT(1A) receptors. Nevertheless the initiation of the 'micturition reflex' involves the activation of 5-HT(1A) receptors.

Evaluation of impaired dynamic cerebral autoregulation by the Mueller manoeuvre.

Arterial blood pressure (ABP) shows polyphasic changes during the Mueller manoeuvre (voluntary negative intrathoracic pressure). The aim of the present study was to investigate (1) whether these changes could be applied to detect impaired dynamic cerebral autoregulation (dCA) in carotid stenosis and (2) whether the degree of indicated impairment correlates with transfer function phase as another current measure for dCA (deep breathing method) and CO2-reactivity. We examined 13 patients with severe unilateral carotid artery stenosis and 16 age-matched controls during 15-s Mueller manoeuvres (MM) at -30 mmHg using bilateral transcranial Doppler sonography and non-invasive ABP recordings (Finapres, 2300, Ohmeda, Englewood, CO, USA). After an initial biphasic oscillation, cerebral blood flow velocity (CBFV) and ABP decreased to below baseline. CBFV reincreased in controls and on contralateral sides in patients 6.0 s (3.8-9.5 s, median and range) after the onset of the decrease, despite a further fall in ABP. CBFV over the affected side revealed a significantly delayed reincrease (8.0 (5.6-10.3) s; P<0.01) combined with a relatively flat and inertial amplitude behaviour. An applied autoregulation index derived from the MM (mROR), phase shift and CO2-reactivity were severely reduced on the affected side in patients (P<0.01). Reduction of the mROR correlated significantly with reduction of phase shift (r=0.69; P=0.002) and CO2-reactivity (r=0.78; P=0.002). In conclusion, the different cerebral haemodynamic pattern during the MM in patients is likely to reflect impaired dCA. The degree of indicated impairment correlates with that of transfer function phase and CO2-reactivity. Therefore, the MM represents a convenient method for grading of compromised cerebral haemodynamics in patients with carotid artery stenosis.

Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans

Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1.1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P = 0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P = 0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P = 0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.

Effect of inhibition of nitric oxide synthase on dynamic cerebral autoregulation in humans

Cerebral blood flow is maintained constant over a range of cerebral perfusion pressures by cerebral autoregulation. Impaired cerebral autoregulation may be important in the pathogenesis of cerebral ischaemia. The mechanisms mediating normal cerebral autoregulation in humans are poorly understood. We used a recently described transcranial Doppler technique, which allows non-invasive measurement of dynamic cerebral autoregulation, to test the hypothesis that nitric oxide mediates cerebral autoregulation. The rate of rise of middle cerebral artery blood flow velocity, compared with that of arterial blood pressure, was determined following a stepwise fall in arterial blood pressure, in order to calculate an autoregulatory index. The effect of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA) on dynamic autoregulation was compared with that of noradrenaline titrated to result in a similar rise in blood pressure. Six healthy subjects were studied in each group. The mean (S.D.) change in autoregulatory index following noradrenaline at a similar pressor dose was significantly greater than the change following the L-NMMA bolus: 1. 1 (1.2) compared with -0.8 (0.8) for the left middle cerebral artery (P=0.002), and 1.1 (0.8) compared with -0.8 (0.8) for the right middle cerebral artery (P=0.002). There was no difference in the mean (S.D.) blood pressure increase resulting from the two agents: L-NMMA, 19.7 (7.4) mmHg; noradrenaline, 15.5 (4.8) mmHg (P=0.281). These results suggest that nitric oxide mediates at least part of the dynamic phase of cerebral autoregulation in humans. Reduced nitric oxide release may play a role in the impaired cerebral autoregulation seen in patients with, or at risk of, cerebral ischaemia.

Hypotensive action of coumarin glycosides from Daucus carota.

Daucus carota (carrot) has been used in traditional medicine to treat hypertension. Activity-directed fractionation of aerial parts of D. carota resulted in the isolation of two cumarin glycosides coded as DC-2 and DC-3. Intravenous administration of these compounds caused a dose-dependent (1-10 mg/kg) fall in arterial blood pressure in normotensive anaesthetised rats. In the in vitro studies, both compounds caused a dose-dependent (10-200 microg/ml) inhibitory effect on spontaneously beating guinea pig atria as well as on the K+ -induced contractions of rabbit aorta at similar concentrations. These results indicate that DC-2 and DC-3 may be acting through blockade of calcium channels and this effect may be responsible for the blood pressure lowering effect of the compounds observed in the in vivo studies.

Baroreceptor control of heart rate in the awake toad: peripheral autonomic effectors and arterial baroreceptor areas

Systemic injection of sodium nitroprusside (30 μg/kg, i.v.) in the awake Bufo paracnemis toad induced a fall in arterial blood pressure and tachycardia. This tachycardia, but not the hypotension, was significantly reduced in toads with bilateral electrolytic lesion of the caudal and commissural regions of the solitary tract nucleus and in animals with transection of the spinal cord, 2 mm below the obex. This indicates that the tachycardia is reflex, depends on the integrity of the solitary tract nucleus and is due to descending spinal autonomic activation. Pretreatment with propranolol (4 mg/kg, i.v.) significantly reduced the tachycardia but did not block it completely, showing the importance of beta-adrenoceptors in its genesis. The reflex increase in heart rate induced by nitroprusside was not statistically significant in animals with bilateral section of the laryngeal nerve, whose baroreceptor fibers originate from the pulmocutaneous artery or in animals in which the bilateral section of the laryngeal nerve was performed together with section of the glossopharyngeal nerves, which incorporate fibers originating from the carotid labyrinth. The reduction of the reflex tachycardia was significant in toads with aortic arch denervation alone or combined with section of the laryngeal nerves or in animals with complete denervation of the three baroreceptors areas. These results suggest that the region of the aortic arch, when submitted to unloading, is the most important baroreceptor zone for cardiac compensation in toads.

Medial prefrontal cortex acetylcholine injection-induced hypotension: the role of hindlimb vasodilation

The injection of acetylcholine (ACh) into the cingulate region of the medial prefrontal cortex (MPFC) causes a marked fall in arterial blood pressure which is not accompanied by changes in heart rate. The purpose of the present study was to investigate the hemodynamic basis for this stimulus-induced hypotension in Sprague–Dawley rats. The study was designed to determine whether a change in the vascular resistance of hindlimb, renal or mesenteric vascular beds contributes to the fall in arterial pressure in response to ACh injection into the cingulate cortex. Miniature pulsed-Doppler flow probes were used to measure changes in regional blood flow and vascular resistance. The results indicated that the hypotensive response was largely due to a consistent and marked vasodilation in the hindlimb vascular bed. On this basis, an additional experiment was then undertaken to determine the mechanisms that contribute to hindlimb vasodilation. The effect of interrupting the autonomic innervation of one leg on the hindlimb vasodilator response was tested. Unilateral transection of the lumbar sympathetic chain attenuated the cingulate ACh-induced vasodilation in the ipsilateral, but not in the contralateral hindlimb. These results suggest that the hypotensive response to cingulate cortex-ACh injection is caused by skeletal muscle vasodilation mediated by a sympathetic chain-related vasodilator system.

Studies on antihypertensive and antispasmodic activities of methanol extract of Acacia nilotica pods.

A methanol extract of Acacia nilotica pods (AN) caused a dose-dependent (3-30 mg/kg) fall in arterial blood pressure. Treatment of animals with atropine abolished the vasodilator response of acetylcholine (ACh), whereas the antihypertensive effect of the plant extract remained unaltered. Phentolamine (an alpha-adrenergic blocker) abolished the vasoconstrictor effect of norepinephrine (NE), whereas pretreatment of the animal with AN, did not modify the NE response. These results indicate that the antihypertensive effect of plant extract is independent of muscarinic receptor stimulation or adrenoceptor blockade. In the in vitro studies, AN produced a dose-dependent (0.3-3.0 mg/mL) inhibitory effect on force and rate of spontaneous contractions in guinea-pig paired atria. Similarly, it inhibited the spontaneous contraction of rabbit jejunum in a concentration-dependent (0.1-3.0 mg/mL) manner. AN also inhibited K(+)-induced contractions in rabbit jejunum at a similar concentration range, which suggests that the antispasmodic action of AN is mediated through calcium channel blockade, and this may also be responsible for the blood pressure lowering effect of AN, observed in the in vivo studies.

Experimental treatment of the acute cardiovascular toxicity of caffeine.

The intravenous infusion of caffeine-sodium salicylate (15 mg/kg/min) into artificially ventilated and anesthetized rats caused a progressive fall in arterial blood pressure which was mainly due to a decrease in peripheral resistance. Cardiac output increased initially by 15% but then declined after 30 minutes. The electroencephalogram showed sinus tachycardia and ectopic beats mainly in the form of monomorphic ventricular bigeminy which began after 22.8 minutes. Fatal ventricular fibrillation occurred in all animals by 66.9 +/- 3.1 minutes. Treatment of cardiac arrhythmia by repeated intravenous injections of propranolol (1 mg/kg) or verapamil (1 mg/kg) was effective and prolonged survival time to 91.7 +/- 4.4 or 84.3 +/- 2.9 minutes, respectively (p < 0.05). Propranolol also prolonged survival time when administered in a single dose of 20 mg/kg i.v. 10 minutes before the initiation of caffeine infusions. Repeated administrations of quinidine sulfate (5 mg/kg), phenytoin (5 mg/kg), or lidocaine (1-5 mg/kg), on the other hand, exerted very short antiarrhythmic activity and did not prolong survival time at all. Fluid therapy with polygeline plasma expander (0.5 mL/kg/min) did not influence caffeine-induced cardiovascular failure in any way. Ventricular ectopia leading to fibrillation accounts for the lethal outcome of caffeine poisoning in anesthetized rats and can be antagonized by treatment with propranolol or verapamil.

The cardiopulmonary effects of clenbuterol when administered to dorsally recumbent halothane-anaesthetised ponies — failure to increase arterial oxygenation

Clenbuterol (0·8 μg kg −1 intravenously) was investigated in ponies (small horses) anaesthetised with acepromazine, detomidine and thiopentone, then halothane in oxygen alone (hyperoxic group) or with nitrous oxide (hypoxic group). Following instrumentation, ponies were placed in dorsal recumbency for 60 minutes, clenbuterol (both groups) or a saline control (hyperoxic group) given, and cardiopulmonary parameters monitored for a further 60 minutes. In the hyperoxic group, clenbuterol administration resulted in a transitory (<five minutes) 15 per cent fall in arterial blood pressure and 78 per cent rise in intramuscular blood flow. Heart rate increased from a mean of 42 (SD 4) to 54 (12) beats per minute, the rise being significant for 15 minutes. Cardiac index increased from 2·1 (0·7) to 3·-9 (0·7) litres m −2 and remained significantly elevated for the remainder of the measurement period. Cardiovascular changes in the hypoxic group were similar. 30 minutes after clenbuterol administration, PaO 2 had changed non-significantly from 32·.3 (19·2) to 33·.4 (17) kPa in the hyperoxic group and from 7·9 (1·8) to 8·.6 (1·3) kPa in the hypoxic group. The study concludes that under these experimental conditions, clenbuterol does not cause significant improvement in arterial oxygenation, but its cardiovascular effects are minimal or advantageous.

Discovery of novel selective hypotensive vasopressin peptides that exhibit little or no functional interactions with known oxytocin/vasopressin receptors.

1. Arginine-vasopressin (VP) has both vasoconstricting and vasodilating action. We report here the discovery of four novel selective hypotensive VP analogues: d(CH2)5[D-Tyr(Et)2,Arg3,Val4]AVP; d(CH2)5[D-Tyr(Et)2,Lys3,Val4]AVP and their iodinatable Tyr-NH2(9) analogues. 2. Bioassays in rats for activities characteristic of neurohypophysial peptides showed that the four VP peptides possessed little or no V1a, V2 or oxytocin (OT) receptor agonistic or antagonistic activities. 3. In anaesthetized rats, these peptides (0.05-0.10 mg kg(-1) i.v.) elicited a marked fall in arterial blood pressure. 4. Blockade of cholinoceptors, adrenoceptors and bradykinin B2 receptors, and inhibition of prostaglandin synthesis had little effect on their vasodepressor action. 5. Classical V1a, V2 and OT receptor antagonists did not block the vasodepressor response. 6. L-NAME, 0.2 mg kg(-1) min(-1), markedly suppressed the hypotensive response to ACh but not the vasodepressor response to the hypotensive VP peptides. However, the duration of the vasodepressor response was shortened. Very high doses of L-NAME attenuated both the vasodepressor response and the duration of action. 7. These findings indicate that the vasodepressor action of these VP peptides is independent of the peripheral autonomic, bradykinin and PG systems and is not mediated by the known classical OT/VP receptors. NO does not appear to have an important role in their vasodepressor action. 8. The discovery of these novel VP peptides could lead to the development of new tools for the investigation of the complex cardiovascular actions of VP and the introduction of a new class of hypotensive agents. The two iodinatable hypotensive VP peptides could be radiolabelled as potential markers for the localization of the receptor system involved.

The role of A3 adenosine receptors in central regulation of arterial blood pressure.

1. Pharmacological studies have suggested that A3 receptors are present on central neurons. Recently this adenosine receptor subtype has been identified in the rat and its presence in the central nervous system has been confirmed. 2. In this study we investigated the effects of acute intracerebroventricular (i.c.v.) injections of N6-2-(4-aminophenyl)-ethyladenosine (APNEA), a non-selective A3 adenosine receptor agonist, on arterial blood pressure (ABP) and heart rate (HR), after treatment with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective antagonist of A1 adenosine receptors. 3. Anaesthetized rats, after DPCPX (12 microg(-1) kg i.c.v.), were treated with APNEA (0.4-4 microg kg(-1) i.c.v.) resulting in a transitory and dose-dependent decrease in arterial blood pressure without a change in heart rate. APNEA also induced hypotensive responses after i.c.v. pretreatment with aminophylline, at a dose of 20 microg kg(-1). In contrast, pretreatment 48 h before, with 4 microg kg(-1) i.c.v. of pertussis toxin reduced the hypotensive effect induced by APNEA. Administration of APNEA at a higher dose (20 microg kg(-1) i.c.v.), after DPCPX, induced a decrease in ABP of -66+/-5.4 mmHg and after 3 min a decrease in heart rate of -62+/-6.0 beats min(-1). Transection of the spinal cord abolished this significant fall in ABP, but not the decrease of HR. 4. These results suggest that a population of A3-receptors is present in the CNS, whose activation induces a decrease in blood pressure with no change of heart rate.

Purification and Cardiovascular Activity of [Met 1, Met 5]-Bradykinin from the Plasma of a Sturgeon (Acipenseriformes)

The sturgeons (Order Acipenseriformes) are extant representatives of a group of primitive Actinopterygian (ray-finned) fish that probably shared a common ancestor with present-day teleosts. Incubation of heat-denatured plasma from a sturgeon (a hybrid of the shovelnosed sturgeon Scaphirhynchus platorynchus and the pallid sturgeon Scaphirhynchus albus) with either trypsin or porcine pancreatic kallikrein generated bradykinin-like immunoreactivity. The primary structure of sturgeon bradykinin was established as Met-Pro-Pro-Gly-Met-Ser-Pro-Phe-Arg. This amino acid sequence contains two amino acid substitutions (Arg 1 → Met and Phe 5 → Met) compared with mammalian bradykinin. Bolus injections of synthetic sturgeon bradykinin in doses as low as 1 pmol/kg into the dorsal aorta of unanesthetized sturgeon resulted in an immediate and significant fall in arterial blood pressure with a maximum depressor response at 300 pmol/kg. Thus, the cardiovascular response of the sturgeon to bradykinin resembles more closely the response of mammals rather than the predominantly pressor response seen in teleost fish. Sturgeon bradykinin produced a strong and concentration-dependent (EC 50 = 4.7 ± 0.7 × 10 −10 M) relaxation of rings of vascular tissue from the sturgeon ventral aorta that had been pre-contracted with acetylcholine. The data indicate that sturgeon tissues are particularly responsive to native bradykinin and suggest that the kallikrein–kinin system may have evolved before the appearance of the neopterygians (gars, bowfin and teleosts).

Atrial natriuretic peptide and mechanisms of cardiovascular control. Role of serotonergic receptors.

Atrial natriuretic peptide (ANP) inhibits renal sympathetic nerve activity (RSNA), provided the vagi are intact. Afferents from chemosensitive cardiopulmonary receptors are specifically required. Such receptors produce the Bezold-Jarisch reflex, are prominent on the ventricular epicardium, and are richly supplied with 5-hydroxytryptamine type 3 (5-HT3) receptors. We tested the hypothesis that epicardial 5-HT3-sensitive neurons mediate depressor effects of ANP. Through a special catheter, anesthetized, sinoaortically denervated rats received pericardial test injections of ANP (28-amino acid rat ANP; 100 and 1,000 ng) in the presence or absence of 5-HT3 antagonist (Ondansetron, 20 micrograms/kg; n = 9). In other groups we observed the effects of systemic ANP while blocking either epicardial or systemic 5-HT3 receptors. Arterial blood pressure (ABP), heart rate, and RSNA were recorded continuously. Intravenous ANP (100 or 200 ng) decreased ABP and RSNA significantly. In contrast, intrapericardial ANP (100 or 1,000 ng) caused no significant fall in ABP or RSNA. Both intravenous and pericardial Ondansetron reduced the effects of intravenous ANP significantly, but the intravenous antagonism was significantly greater. We conclude that epicardial chemosensitive afferents are not sensitive to ANP and that sympathoinhibitory effects of ANP arise from a 5-HT3 agonist that cannot be produced when ANP is confined to the pericardial space.