[The sympathetic baroreflex is enhanced during emotional stress in rats]. / Sensibilisation du baroréflexe sympathique durant le stress émotionnel chez le rat.

The sympathetic component of the baroreceptor reflex might play a major role in limiting hypertensive effects of emotional stress. However, it has been suggested that this type of stress inhibits or even suppresses the baroreflex. The aim of the present study was, therefore, to determine the effects of emotional stress on the sympathetic baroreflex in conscious rats. In 11 Sprague Dawley rats, arterial pressure (AP) and renal sympathetic nerve activity (RSNA) were recorded simultaneously before and during exposure to a mild emotional stressor (jet of air). Under both conditions, baroreflex function curves relating AP and RSNA were constructed by fitting a sigmoid function to RSNA and AP measured during sequential nitroprusside and phenylephrine administrations. Air-jet stress significantly (P<0.01) increased the mean levels of AP (from 112 +/- 2 to 124 +/- 2 mmHg), heart rate (from 381 +/- 10 to 438 +/- 18 beats/min) and RSNA (from 0.80 +/- 0.14 to 1.49 +/- 0.23 microV). Sympathetic baroreflex function curves were shifted to a higher level of AP, and this was accompanied by an increase (P<0.01) in the maximum gain (from 9.0 +/- 1.3 to 16.2 +/- 2.1 normalized units (NU)/mmHg). The latter effect was a consequence of an increase (P<0.01) in the maximal range of variations of RSNA (from 285 +/- 33 to 619 +/- 59 NU). Finally, the operating range of the sympathetic baroreflex, which corresponds to the AP range over which the reflex is able to alter RSNA, was increased (from 34 +/- 2 to 41 +/- 3 mmHg; P<0.01). In conclusion, the baroreflex control of RSNA is sensitized and operates over a larger range during emotional stress in rats, which suggests that renal vascular tone, and possibly AP, are very efficiently controlled by the sympathetic nervous system under this condition.

Cardiovascular effects of the N-methyl-D-aspartate receptor antagonist MK-801 in conscious rats.

Evidence from microinjection studies in anesthetized rats suggests that central excitatory amino acid pathways using N-methyl-D-aspartate receptors are involved in the regulation of the cardiovascular system. To test the hypothesis that these pathways are tonically involved in the maintenance of or the baroreceptor reflex regulation of cardiovascular function, we have examined the effects of intravenous injection of the centrally acting, noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), on the mean arterial pressure, heart rate, renal sympathetic nerve activity, and behavior of conscious, freely moving sham-operated and sinoaortic baroreceptor-denervated rats. Administration of MK-801 produced, within 5 minutes, dose-dependent elevations in mean arterial pressure, heart rate, and renal sympathetic nerve activity that were sustained for 0.5 to 2.5 hours. For an equivalent dose, MK-801 produced approximately twice the peak changes in mean arterial pressure and heart rate in the sinoaortic baroreceptor-denervated rats than in the sham-operated rats. Pretreatment results were as follows: 1) The ganglion blocker chlorisondamine markedly attenuated the hypertension and tachycardia in the sham-operated and sinoaortic baroreceptor-denervated rats, 2) pretreatment with the alpha 1-adrenergic receptor antagonist prazosin virtually abolished the hypertension, and 3) the beta 1-adrenergic receptor antagonist atenolol markedly reduced the tachycardia. MK-801 also produced stereotypic behaviors and ataxia in the sham-operated and sinoaortic baroreceptor-denervated rats; however, qualitatively and quantitatively similar changes in behavior were induced in the latter by doses approximately five time lower than required in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Synthetic neoglycolipids for biological applications: correlation between their structures and their interactions with membrane proteins.

Synthetic glycolipids are of interest for their biological applications requiring interactions with membrane proteins. Depending on their structures, new series of glycolipids have applications in extraction of membrane proteins or medical applications as mimics of natural ligands of proteins.

High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.

OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. METHODS: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin:glucose ratio, but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.

Cardiovascular effects of two new calcium antagonists, PY 108-068 and PN 200-110, in conscious spontaneously hypertensive rats.

1. The acute cardiovascular effects of PY 108-068 and PN 200-110 were studied by means of a computerized analysis of the intra-aortic blood pressure (BP) recorded continuously for 26 h in conscious unrestrained spontaneously hypertensive rats. Both compounds were studied at three doses (50, 100 and 200 micrograms kg-1) and each dose was administered intravenously 5 times (09 h 00 min, 14 h 00 min, 19 h 00 min, 24 h 00 min and 09 h 00 min). Baroreflex sensitivity was measured 1 h following the last injection. 2. The two compounds were found to induce rapid (3 min) and dose-dependent falls in BP. After the first administration, these decreases reached -20% and -35% for systolic BP (SBP) and diastolic BP (DBP) respectively with PY 108-068 (200 micrograms kg-1) and -25% and -45% for SBP and DBP respectively with PN 200-110 (200 micrograms kg-1). 3. The duration of the reduction in BP increased with the dose and was much longer for PN 200-110 (180 min for SBP) than for PY 108-068 (20 min for SBP). 4. A tachycardia was associated with the decrease in BP which did not differ at 200 micrograms kg-1 between PY 108-068 (+ 108 beats min-1) and PN 200-110 (+ 103 beats min-1). Baroreflex sensitivity was not significantly increased by either drug. 5. The 5 repeated injections of PY 108-068 and PN 200-110 evoked similar responses. 6. In conclusion, both compounds exhibited marked hypotensive properties. PN 200-110 appeared to be more suitable for further development since its effects were found to be greater and much longer lasting than those of PY 108-068.

Sympathoinhibitory effects of rilmenidine may be mediated by sites located below the brainstem.

1. To determine the site of action of rilmenidine, we examined its effets on arterial blood pressure (BP), heart rate (HR) and postganglionic renal sympathetic nerve activity (RSNA) after intracerebroventricular (i.c.v.) administration (300 micrograms kg-1), in groups (all n = 6) of conscious and freely moving, pentobarbitone-anaesthetized and pentobarbitone-anaesthetized and spinally transected, fifteen week-old male spontaneously hypertensive rats (SHRs). 2. In conscious SHRs, which exhibited a low sympathetic nerve activity (RSNA: 3.4 +/- 0.9 muV), rilmenidine was inactive on systolic BP (SBP), diastolic BP (DBP), HR and RSNA. 3. In intact pentobarbitone-anaesthetized SHRs, which exhibited an elevated sympathetic nerve activity (RSNA: 10.6 +/- 0.9 muV), rilmenidine exerted potent antihypertensive (delta SBP: -37 +/- 4%; delta DBP: -43 +/- 6%), bradycardic (delta HR: -32 +/- 3%) and sympathoinhibitory (delta RSNA: -68 +/- 9%) activities. 4. In pentobarbitone-anaesthetized SHRs with cervical spinal cord transection, BP was markedly decreased and sympathetic nerve activity (RSNA: 10.3 +/- 3.1 muV) returned to the level observed in conscious SHRs (RSNA: 3.6 +/- 0.5 muV). In these conditions, rilmenidine remained sympathoinhibitory (delta RSNA: -74 +/- 5%). 5. In conclusion, we have shown that pentobarbitone-anaesthesia enhances the peripheral sympathetic tone by a central action, as the spinal cord transection allows RSNA to return to normal levels and that, spinal or ganglionic structures could be a major site of the sympathoinhibitory action of rilmenidine.

Effect of desipramine on spontaneous arterial pressure oscillations in the rat.

There has been no previous report on the effect of the noradrenaline uptake inhibitor desipramine on short-term variability of arterial pressure. Mean arterial pressure was recorded in 9 conscious resting rats during 4 consecutive 30-min periods: (1) under baseline conditions, (2) after desipramine administration (2 mg/kg i.v., followed by 1 mg/kg every hour), then after (3) cardiac autonomic blockade with methylatropine and atenolol, and (4) alpha-adrenoceptor blockade with phentolamine. Fast Fourier transform analysis was applied to beat-to-beat data after resampling at 10 Hz of consecutive 205-s time series. Desipramine did not change the mean level and overall variability of mean arterial pressure. However, spectral power in the mid-frequency (0.3-0.5 Hz) band containing the Mayer waves was reduced by more than 80%, and power in the low-frequency (0.05-0.2 Hz) band was enhanced by approximately 50%, especially due to the appearance of a major oscillation centred at 0.095 +/- 0.005 Hz. This slow oscillation was further enhanced after cardiac autonomic blockade and was abolished after alpha-adrenoceptor blockade. In conclusion, desipramine profoundly alters short-term arterial pressure variability in resting rats, mainly by shifting vasomotor waves from 0.4 to 0.1 Hz. Desipramine may prove a valuable pharmacological tool to study the dynamic aspects of arterial pressure control.

How sympathetic tone maintains or alters arterial pressure.

After chronic sympathectomy or sinoaortic denervation (SAD), arterial pressure (AP) becomes extremely unstable, especially because of movement-related depressor episodes. The simultaneous measurement of AP and regional blood flows in sympathectomized and SAD rats indicates that these depressor episodes are accompanied by strong regional vasodilations, possibly involving an autoregulatory component. The sympathetic nervous system, mainly through baroreflex modulation of its activity, overrides these responses and thereby, considerably limits the AP variability. In the conscious unrestrained rat, AP fluctuates in a narrow range (variation coefficients calculated over 1-hour beat-to-beat recordings are typically approximately 5%). This variability of AP involves sympathetically-mediated pressor episodes that are coupled to behavior and alerting environmental stimuli. Regarding the latter, studies in SAD rats point to an opposing interaction between centrally-induced sympathoexcitation and baroreflex activation. Another component of normal AP variability appears as an oscillation centered around 0.4 Hz. Spectral analysis of AP and regional hemodynamic variables indicates that this oscillation is secondary to rhythmic fluctuations in the vasomotor sympathetic tone that are synchronized by the arterial baroreceptor reflex. It is concluded that both stability and normal variability of AP critically depend on the baroreflex control of the sympathetic vascular tone.

Soman-induced hypertension in conscious rats is mediated by prolonged central muscarinic stimulation.

The acetylcholinesterase inhibitor, soman, induces marked and sustained hypertension and tachycardia associated with a convulsive syndrome in rats. The aims of the present study were to distinguish between the cardiovascular and convulsant effects of soman and to determine whether the maintenance of the soman-induced hypertension and tachycardia depends solely on a central muscarinic effect. To this end, using a computerised analysis of blood pressure (BP) in conscious freely moving rats, we examined the consequences on the increase in mean BP (MBP) and heart rate (HR) induced by soman (60 micrograms/kg, i.v.) of 1) a pre-treatment with the anticonvulsant drug diazepam (3 mg/kg, i.v.) and 2) atropine sulphate (10 mg/kg, i.v.) administered 10 or 60 min after the intoxication. Pretreatment with diazepam prevented the convulsions, assessed by electroencephalogram (EEG) recording, but modified neither the magnitude nor the kinetics of the pressor and tachycardic effects of soman (delta MBP = 74 +/- 2 and 73 +/- 5 mmHg, delta HR = 69 +/- 10 and 79 +/- 7 bpm, maximum MBP = 186 +/- 3 and 182 +/- 6 mmHg, maximum HR = 545 +/- 9 and 522 +/- 16 bpm in solvent- (n = 8) and diazepam- (n = 8) pre-treated rats, respectively). Whatever its time of administration, atropine sulphate fully and immediately reversed the rise in BP induced by soman. The soman-induced tachycardia was also suppressed by atropine administered 10 min after soman whereas it persisted when atropine was injected 60 min after the intoxication. These results show that the cardiovascular effects of soman can occur independently of the convulsive syndrome and that the maintenance of the soman-induced hypertension depends entirely on a permanent central muscarinic stimulation.

Studies on neural and humoral contributions to arterial pressure lability.

The mechanisms of arterial pressure lability in rats following sinoaortic deafferentation (SAD) remain unknown. In this paper, we review several studies that have investigated the potential mechanisms of this lability. Combined ganglionic and alpha-adrenergic receptor blockade reduced lability but not to control levels, indicating that the sympathetic nervous system plays a major role but is not the only mechanism involved in the generation of lability. When ganglionic blockade was combined with blockade of an endogenous humoral vasoconstrictor (vasopressin or angiotensin), lability was returned to control levels in SAD rats; however, humoral blockade alone did not alter lability. Infusion of phenylephrine or endogenous vasoconstrictors in the presence of combined neural and humoral blockade increased arterial pressure lability to levels similar to those found in rats with SAD. The neurogenic contribution to lability was further investigated by recording renal sympathetic nerve activity in conscious freely moving intact rats and rats with SAD. These studies demonstrated that one day after SAD, there was little direct correlation between transient changes in renal sympathetic nerve activity and arterial pressure lability. Thus, the evidence presented in this paper is consistent with the hypothesis that arterial pressure lability is not the direct result of unbuffered variations in sympathetic discharge but rather is produced by an interaction between neural and humoral components.

[Origin and role of circulating catecholamines in the normotensive sympathectomized rat]. / Origine et rôle des catécholamines circulantes chez le rat normotendu sympathectomisé.

Early chronic treatment with guanethidine destroys peripheral sympathetic nerves while sparing the adrenal medulla, and does not lower blood pressure (BP) in conscious normotensive rats (Julien et al. Am J Physiol 1990; 259: H1337). Therefore, the origin and role of circulating catecholamines (CAs) in BP maintenance were examined in conscious normotensive control, sympathectomized (SNX)--daily s.c. injections of guanethidine from 1 to 13 weeks of age--and sympathectomized-adrenalectomized (SNX-A) rats by measuring i) their plasma CAs (norepinephrine, NE and epinephrine, E) and 3,4-dihydroxyphenylglycol (DHPG) by HPLC-FD, and ii) their mean BP (MBP) responses to phenylephrine and phentolamine (5 mg/kg i.v.). The doses of phenylephrine that produced similar MBP rises were 3 micrograms/kg in controls (44 +/- 4 mmHg) and 1.5 micrograms/kg in SNX (47 +/- 3 mmHg) and SNX-A (48 +/- 2 mmHg) rats. Results are as follows: [table: see text] In conclusion, in conscious normotensive SNX rats: (1) most of the circulating NE is of adrenomedullary origin and plasma DHPG derives from neuronal NE; (2) due to supersensitivity of the cardiovascular system, stimulation of alpha-adrenoreceptors by circulating CAs play a significant role in BP maintenance.

[Autoregulation of renal blood flow and blood pressure variability in the conscious rat]. / Autorégulation du débit sanguin rénal et variabilité tensionnelle chez le rat éveillé.

It is often proposed that autoregulatory mechanisms prevent acute changes in systemic blood pressure (BP) from being transmitted to the glomerular capillary circulation. However, it is not known whether renal blood flow (RBF) is still autoregulated when the kidney is exposed to exaggerated BP fluctuations, in particular hypertensive episodes. The aim of the present study was therefore to evaluate the efficacy of renal autoregulatory responses in an animal model of BP lability, the sinoaortic denervated (SAD) rat. BP and RBF were simultaneously recorded in 8 SAD (2 wks before study) and 8 baroreceptor intact (INT) Sprague-Dawley rats during approximately 3 h of spontaneous activity. The left kidney used for RBF recordings was denervated to prevent the interference of changes in renal sympathetic tone with autoregulatory responses. The SAD procedure modified neither the mean BP nor the mean RBF levels (111 +/- 1 mmHg and 11.3 +/- 1.3 mL/min in INT rats: 113 +/- 6 mmHg and 11.1 +/- 0.9 mL/min in SAD rats). However, SAD strongly increased the BP variability (coefficient of variation: 5.9 +/- 0.2% and 18.2 +/- 1.1% in INT and SAD rats, respectively). In spite of this marked BP lability, RBF variability was not significantly affected by the SAD procedure (9.1 +/- 0.8% and 12.4 +/- 1.6% in INT and SAD rats, respectively). In SAD rats, spontaneous hypertensive episodes (top 1% of BP values: 174 +/- 10 mmHg) did not induce increases in RBF (10.5 +/- 1.0 ml/min). Fast Fourier transform analysis revealed that in SAD rats, autoregulatory mechanisms attenuated approximately 80% of BP fluctuations in the 0.0015-0.01 Hz frequency range, suggesting a major involvement of the tubuloglomerular feedback. In conclusion, autoregulatory mechanisms have an ample capacity to protect the kidney against spontaneous BP fluctuations in the conscious rat. Consequently, BP variability per se is probably not detrimental to the kidney, as long as autoregulatory mechanisms are normally functioning.

[Role of renin-angiotensin system and vasopressin in the control of blood pressure in genetically hypertensive rats after sympathectomy]. / Rôle du système rénine angiotensine et de la vasopressine dans le contrôle de la pression artérielle chez le rat génétiquement hypertendu après sympathectomie.

Early chronic sympathectomy does not normalize blood pressure (BP) in genetically hypertensive rats of the Lyon strain (LH). The purpose of this study was to examine the role of the renin angiotensin system (RAS) and vasopressin in the residual hypertension exhibited by LH sympathectomized rats. Chronic sympathectomy was achieved by treating male LH and control normotensive LN rats with guanethidine sulfate between 1 and 13 weeks of age (60 mg/kg daily from day 7 after birth to day 25, 30 mg/kg daily from day 26 to day 70 and 30 mg/kg every other day from day 71 to day 90). At 14 weeks of age, catheters were inserted into the lower abdominal aorta and inferior vena cava via the left femoral artery and vein. After 2 days of recovery, BP was continuously recorded in the conscious freely moving animals during 3 consecutive 1-hour periods: before and after administration of either an angiotensin converting enzyme inhibitor (perindopril 2 mg/kg i.v.) or a selective vascular vasopressin antagonist [beta-mercapto- beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2, Arg8-vasopressin, AVPX 10 micrograms/kg i.v.) and finally after conjoint administration of both drugs. At the end of each period, the efficacy of blockade was verified by the disappearance of pressor responses to respective agonists (angiotensin I 150 ng/kg i.v., Arg8-vasopressin 10 ng/kg i.v.). Chronic treatment with guanethidine resulted in the disappearance of pressor responses to tyramine (250 micrograms/kg i.v.) indicating complete functional denervation of the vessels. Under basal conditions, the 1-hour average value of mean BP (MBP) was higher in LH than in LN sympathectomized rats (134 +/- 3 vs 104 +/- 2 mmHg, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Role of sympathetic nerve fibers in hemodynamic responses to stress in rats]. / Rôle des fibres nerveuses sympathiques dans les réponses hémodynamiques au stress chez le rat.

Hemodynamic responses to acute stress exposure were studied in normotensive control (C) and chronically sympathectomized (S) rats. Male Sprague-Dawley rats received daily sc injections of either saline (C) or guanethidine (S) from 1 to 13 weeks of age. Doppler flow probes were then implanted for the measurement of blood velocity in the sub-diaphragmatic aorta, superior mesenteric artery and distal aorta (hindquarters). After 10 days of recovery and 24 hours before the study, the caudal artery was cannulated. In the conscious freely moving rats, mean arterial pressure (MAP), heart rate (HR) and indices of regional blood flows and vascular conductances (G as blood flow/MAP ratio) were recorded beat to beat, before and during emotional stress (jet of air for 2 min). In basal conditions, mean values of MAP and HR were similar in C (107 +/- 2 mmHg; 399 +/- 8 bpm, n = 9) and S (106 +/- 3 mmHg; 384 +/- 12 bpm, n = 7) rats. The effects of stress on MAP, HR, aortic (AoG), mesenteric (MeG) and hindquarters (HqG) vascular conductances are expressed as percentage changes from baseline (delta): [table: see text] These results highlight the role of vascular sympathetic nerves in pressor responses and systemic and mesenteric vasoconstrictions induced by stress in the rat. They also indicate that vasodilatation in the hindquarters vascular bed is not secondary to withdrawal of sympathetic vasoconstrictor tone but rather to active phenomena which do not involve the stimulation of vascular beta 2-adrenoceptors by neuronal catecholamines nor the release of vasodilator cotransmitters from the sympathetic nerve endings.

[Sensitivity of the cardiac baroreflex in genetically hypertensive rats of a Lyons strain]. / Sensibilité du baroréflexe cardiaque chez les rats génétiquement hypertendus de souche lyonnaise.

To determine precisely the influence of high blood pressure and age on the baroreflex sensitivity (BRS), we measured it in conscious genetically hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strains. Groups of male rats were studied at the age of 5, 9, 13, 21 and 40 weeks. Using our previously described technique, their blood pressure (BP) and heart period (HP) were recorded beat by beat, in the conscious unrestrained state. Each animal received 2 or 3 i.v. injections of phenylephrine (PHE, 5 micrograms/kg) and nitroglycerin (NG, 100 micrograms/kg). The BRS (msec/mmHg) was computed as the slope of the closest relationship found between systolic BP (SBP) and HP changes. Otherwise, in the 13-week-old rats, BRS had been measured in basal conditions, after vagal blockade (atropine: 2 mg/kg i.v.) and after beta-adrenergic blockade (propranolol: 2 mg/kg) so as to determine the relative importance of vagal and sympathetic components of the baroreflex. In LN and LL rats, the BRS measured with PHE and NG increased markedly between 5 and 9 weeks of age and then remained stable in LN rats or decreased between 21 and 40 weeks of age in LL rats. In LH rats, BRS remained stable between 5 and 9 weeks of age and increased slightly up to 21 weeks of age. Significant differences between LH and LN rats were observed starting from 9 weeks of age when BRS was measured with PHE and only at 9 weeks of age when it was measured with NG injections. In 13-week-old rats, the cardiac baroreflex response was estimated to depend for 82 p. 100 and 18 p. 100 upon vagal and sympathetic components respectively when BRS was measured with PHE injections and of 68 p. 100 and 32 p. 100 when it was measured with NG injections.(ABSTRACT TRUNCATED AT 250 WORDS)

[Computerized analysis of cardiovascular activity in the conscious unrestrained rat. Application to the study of a new antihypertensive agent]. / Analyse informatisée de l'activité cardiovasculaire chez le rat conscient et non restreint. Application à l'étude d'un nouvel antihypertenseur.

A more precise knowledge of cardiovascular activity in rats needs its direct recording for long periods of time, in conscious unrestrained animals. A system has been developed, which allows direct recording of blood pressure (BP) in freely moving rats, by means of a floating catheter chronically inserted in the abdominal aorta, connected to a rotating swivel, and then to a pressure transducer. A mini-computer performs on-line processing of BP curves, and stores the values of 5 cardiovascular parameters on hard disk: systolic, diastolic and mean arterial pressures, heart rate and dp/dt max. Off line processing allows graphic and statistical analysis of the data. Simultaneously recording from two rats is very useful in pharmacology because a treated animal and a control one are studied at the same time and in the same conditions. This methodology was used to evaluate the effects of a chronic treatment (2 mg/kg, ip, during 8 days) and of single injections (0.5 and 3 mg/kg, iv) of a new antihypertensive substance, CM 40441a, in 15 W old males SHR.

[The sympathetic and renin-angiotensin systems are complementary in blood pressure regulation]. / Les systèmes sympathique et rénine angiotensine se complètent pour contrôler la pression artérielle.

The consequences of a chronic destruction of sympathetic nerves or of the blockade of the renin angiotensin system (RAS) on the blood pressure (BP) level and its spontaneous variability were studied using a computerized method which allows a continuous monitoring of BP in conscious unrestrained rats. Guanethidine, used to lesion the sympathetic fibres did not alter the BP level but significantly enhanced its variability. On the opposite, angiotensin converting enzyme inhibition decreased the BP level without changing its variability. It is concluded that both systems play a complementary role as the RAS determines the long-term BP level while the sympathetic nerves control its short-term variability in conscious animals.

Cardiovascular effects of S 9490-3, a new converting enzyme inhibitor: a computerized study in conscious spontaneously hypertensive rats.

The acute cardiovascular effects of S 9490-3, a new angiotensin converting enzyme (ACE) inhibitor, were studied by means of a computerized analysis of the intra-aortic blood pressure (BP), recorded continuously for 48 h in conscious, unrestrained, adult spontaneously hypertensive rats (SHR). The first 24-h recording period was used as a control. On the second day, the rats received a single intravenous (i.v.) injection of S 9490-3 (0.2 mg/kg) at 11 a.m. followed by another 2 mg/kg i.v. injection at 3 p.m. Cardiovascular activity was studied up to 8 a.m. the next day. No significant cardiovascular effects appeared after the 0.2 mg/kg dose, whereas the 2 mg/kg dose induced a rapid fall in systolic and diastolic BP, which remained significant for about 11 h. This BP decrease was not associated with any elevation in heart rate, but with a short lasting increase in dP/dt max. These results are in good agreement with those already obtained with S 9490-3 in various experimental conditions. They suggest that long-term recordings of intra-arterial BP in freely moving rats is of value in the study of drugs which act on the cardiovascular system.

Left atrial endocardial fibrosis and intra-atrial thrombosis - landmarks of left atrial remodeling in rats with spontaneous atrial tachyarrhythmias.

INTRODUCTION: Histological abnormalities are common findings in the left atria (LA) of atrial fibrillation (AF) patients. We aimed to assess LA histological abnormalities in our model of spontaneous atrial tachyarrhythmias in rats. MATERIALS AND METHODS: LA sampling was performed in 12 spontaneously hypertensive rats (SHRs) and eight age-matched Wistar-Kyoto (WKY) rats. Tissue sections were stained with Masson's trichrome and Hematoxylin-Eosin-Safran and examined with a light microscope. A 0 to 3 scoring system was used to quantify the severity of LA structural abnormalities. LA von Willebrand factor (vWF) content was also assessed using immunohistochemical staining. RESULTS: In six of the eight SHRs, LA fibrosis, inflammatory infiltrates, and myocyte necrosis of varying grades of severity were observed. The most frequent feature was endocardial fibrosis, which was observed in six SHRs and in none of the WKY rats. Intra-atrial thrombosis was found in three SHRs and in none of the WKY rats. The intensity of vWF-related fluorescence was higher in the atrial endocardium of SHRs compared to age-matched WKY rats. CONCLUSIONS: Our findings reinforce the role of LA structural abnormalities in atrial arrhythmogenicity. However, two SHRs did not present LA histological abnormalities despite the presence of arrhythmias. This finding suggests that the LA remodeling-atrial tachyarrhythmia relationship could be highly nonlinear and that atrial fibrosis is more likely to be a facilitator of atrial arrhythmogenicity, rather than a prerequisite. We also provide evidence that intra-atrial thrombosis accompanies LA structural remodeling in arrhythmic rats. Increased endocardial platelet adhesion molecule vWF could contribute to this increased thrombogenicity.