Blood pressure variability in established L-NAME hypertension in rats.

METHODS: Blood pressure variability was evaluated in conscious Wistar control rats and rats with established L-NAME hypertension (20 mg/kg per 24 h, 4 weeks). RESULTS: Final systolic arterial pressure was 185+/-5 and 132+/-4 mm Hg in the Nomega-nitro-L-arginine methyl ester (L-NAME)-treated and control rats, respectively. The standard deviation of systolic arterial pressure in the L-NAME group was 70% greater than in the control rats, indicating a significant increase in the overall variability. Arterial pressure in the L-NAME rats exhibited aperiodical, abrupt rises and falls and data was grossly non-stationary. Blood pressure variability was therefore evaluated using Poincaré plot analysis. The variance of the difference (delta) between two successive values of systolic arterial pressure, determined for time intervals of 0.2 to 5 s (0.2 s increment), was always significantly higher in the L-NAME group compared with untreated animals. The variance of delta systolic arterial pressure increased with the time interval and plateaued for time intervals of 2.4 and 1.4 s in hypertensive and normotensive rats, respectively. These differences vanished when the sudden events oberved in L-NAME rats were omitted in the construction of Poincaré plots. Acute administration of prazosin (1 mg/kg), but not losartan (10 mg/kg) markedly reduced the variance of delta systolic arterial pressure in hypertensive rats. CONCLUSIONS: Nitric oxide participates in the control of arterial pressure variability. The sympathetic nervous system seems to be a major determinant of the increased short-term variability of arterial pressure in this model.

[Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism]. / Altérations de la variabilité tensionnelle et cardiaque du rat hyperthyroïdien.

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). Thyrotoxicosis was produced by a daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvant. Autonomic blockers were administered intravenously: atropine (0.5 mg/kg), atenolol (1 mg/kg), atenolol + atropine or prazosin (1 mg/kg). Eight animals were studied in each group. Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423 +/- 6 vs 353 +/- 4 bpm; p < 0.001, unpaired Student's tests), systolic BP elevation (142 +/- 3 vs 127 +/- 2 mmHg; p < 0.001), pulse pressure increase (51 +/- 2 vs 41 +/- 2 mmHg, p < 0.01), cardiac hypertrophy (1.165 +/- 0.017 vs 1.006 +/- 0.012 g, p < 0.001), weight loss (-21 +/- 2 g; p < 0.001) and hyperthermia (37.8 +/- 0.1 vs 37.0 +/- 0.1 degrees C, p < 0.001). The intrinsic HR observed after double blockade (atenolol + atropine) was markedly increased after treatment with thyroxine (497 +/- 16 vs 373 +/- 10 bpm, p < 0.05). Vagal tone (difference between HR obtained after atenolol and intrinsic HR) was positively linearly related to intrinsic HR (r = 0.84; p < 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyrodism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (analyses on 102.4 sec segments, modulus 1.10 +/- 0.07 vs 1.41 +/- 0.06 mmHg; p < 0.01). Prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in experimental hyperthyroidism. Increased intrinsic HR resulting from the direct effect of thyroid hormone on the sinoatrial node is the main determinant of a tachycardia leading to a subsequent rise in cardiac output. The resulting BP elevation could reflexly induce a vagal activation and a sympathetic (vascular and cardiac) inhibition.

Contribution of the autonomic nervous system to blood pressure and heart rate variability changes in early experimental hyperthyroidism.

A great deal of uncertainty persists regarding the exact nature of the interaction between autonomic nervous system activity and thyroid hormones in the control of heart rate and blood pressure. We now report on thyrotoxicosis produced by daily intraperitoneal (i.p.) injection of L-thyroxine (0.5 mg/kg body wt. in 1 ml of 5 mM NaOH for 5 days). Control rats received i.p. daily injections of the thyroxine solvent. In order to estimate the degree of autonomic activation in hyperthyroidism, specific blockers were administered intravenously: atropine (0.5 mg/kg), prazosin (1 mg/kg), atenolol (1 mg/kg) or the combination of atenolol and atropine. A jet of air was administered in other animals to induce sympathoactivation. Eight animals were studied in each group. The dose and duration of L-thyroxine treatment was sufficient to induce a significant degree of hyperthyroidism with accompanying tachycardia, systolic blood pressure elevation, increased pulse pressure, cardiac hypertrophy, weight loss, tachypnea and hyperthermia. In addition, the intrinsic heart period observed after double blockade (atenolol + atropine) was markedly decreased after treatment with L-thyroxine (121.5+/-3.6 ms vs. 141.2+/-3.7 ms, P < 0.01). Of the autonomic indices, vagal tone (difference between heart period obtained after atenolol and intrinsic heart period) was negatively linearly related to intrinsic heart period (r = 0.71, P < 0.05). Atenolol modified neither the heart period nor blood pressure variability in rats with hyperthyroidism and in these rats the jet of air did not significantly affect the heart period level. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of blood pressure variability (analyses on 102.4 s segments, modulus 1.10+/-0.07 vs. 1.41+/-0.06 mm Hg, P < 0.01) and prazosin was without effect on this 0.4 Hz component in these animals. These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic heart rate could be the main determinant of tachycardia. The blood pressure elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Mechanisms of the cardiovascular deconditioning induced by tail suspension in the rat.

The aim of the present work was to obtain insights into the pathophysiology of cardiovascular deconditioning (CVD) induced by tail suspension (TS) in the rat: during TS, when central venous pressure (CVP) has been normalized (E. Martel, P. Champéroux, P. Lacolley, S. Richard, M. Safar, and J. L. Cuche. J. Appl. Physiol. 80: 1390-1396, 1996), and during simulated orthostatism (SO), when transient episodes of hypotension and bradycardia are disclosed, bradycardia with SO represents a response that seems peculiar to the rat compared with humans. According to basic physiology, a reduced activity of the sympathetic system induced by increased CVP was suspected but was not supported by data obtained through spectral analysis of blood pressure (BP) and heart rate (HR) variability or measurements of plasma catecholamine concentration during TS. Nonetheless, indirect evidence was obtained. During SO, plasma catecholamine concentration was lower in TS rats than in controls, suggesting a reduced synthesis of catecholamines, itself secondary to reduced activity of the sympathetic system. Furthermore, after 48 h of TS, the number of binding sites and affinity of alpha-receptors in rat aorta were increased, compatible with a reduced level of neurotransmitter in the synaptic cleft. A second series of experiments was carried out to study hypotension and bradycardia in TS rats during SO. Hypersensitivity of serotonergic mechanisms was suspected. Two 5-HT3 receptor antagonists (ondansetron and MDL-72222) blocked hypotension and restored tachycardia, basic features of orthostatic adaptation of the circulatory system. Response to the 5-HT3 receptor agonist was measured through dose-response curves of BP and HR after injection of 2-methylserotonin. After low doses, hypotension (10 micrograms/kg) and bradycardia (3 and 10 micrograms/kg) were significantly greater in 48-h TS rats than in controls. Thus CVD in the rat induced by TS appears to implicate at least two mechanisms: reduced activity of the sympathetic system and hypersensitivity of serotonergic mechanisms.

Autonomic contribution to the blood pressure and heart rate variability changes in early experimental hyperthyroidism.

OBJECTIVE: To study the interaction between autonomic nervous activity and thyroid hormones in the control of heart rate (HR) and blood pressure (BP). DESIGN AND METHODS: Thyrotoxicosis was produced by injections of L-thyroxine (0.5 mg/kg/day for five days). Blockers were atropine (0.5 mg/kg), atenolol (1 mg/kg) or prazosin (1 mg/kg). Eight animals were studied in each group. Spectral analyses was performed using continuous BP time series obtained in conscious rats. RESULTS: Thyroxine treatment was sufficient to induce a significant degree of tachycardia (423+/-6 vs 353+/-4 bpm, P < 0.001, unpaired Student's t test), systolic BP elevation (142+/-3 vs 127+/-2 mmHg, P < 0.001) and cardiac hypertrophy (1.165+/-0.017 vs 1.006+/-0.012 g, P < 0.001). The intrinsic HR was markedly increased after treatment with thyroxine (497+/-16 vs 373+/-10 bpm, P < 0.05). Vagal tone was positively linearly related to intrinsic HR (r = 0.84, P< 0.01). Atenolol neither modified HR nor BP variability in rats with hyperthyroidism. The thyrotoxicosis was associated with a reduction of the 0.4 Hz component of BP variability (modulus 1.10+/-0.07 vs 1.41+/-0.06 mmHg, P < 0.01). Prazosin was without effect on this 0.4 Hz component in hyperthyroid animals. CONCLUSIONS: These data show a functional diminution of the vascular and cardiac sympathetic tone in early experimental hyperthyroidism. The marked rise in the intrinsic HR could be the main determinant of tachycardia. The BP elevation may reflexly induce vagal activation and sympathetic (vascular and cardiac) inhibition.

Contribution of humoral systems to the short-term variability of blood pressure after severe hemorrhage.

The aim of this study was to generate hemorrhage-triggered fluctuations in blood pressure (BP) at low frequency (LF, < 0.2 Hz) in conscious rats and investigate with spectral analysis the relative roles of hemorrhage-activated catecholamines, the renin-angiotensin system (RAS), and arginine vasopressin (AVP) on the generation of these fluctuations. The individual contribution of these factors was assessed using a combination of the selective antagonists, prazosin, losartan, and Manning compound (AVPX). At rest, systolic BP (SBP) LF fluctuations were slightly increased by losartan. The mid-frequency (MF; 0.2-0.6 Hz) oscillations of SBP and diastolic BP (DBP) were decreased by prazosin alone or associated with AVPX or losartan. The high-frequency (HF; respiratory) oscillations of SBP were increased by prazosin, prazosin plus losartan, and prazosin plus AVPX. After severe hemorrhage (20 ml/kg), the spontaneous BP recovery was characterized by the occurrence of slow fluctuations of SBP and DBP, centered approximately 0.065 Hz, and by increases of MF (89%) oscillations of SBP. The HF component of SBP variability tended to be increased by blood loss. The occurrence of the SBP LF fluctuations was prevented when alpha 1-adrenergic activity was blocked by prazosin. These oscillations were always present, despite inhibition of angiotensin II, and were increased after inhibition of the AVP activity. Pretreatment with the specific inhibitors used in these studies favored the amplifying effect of hemorrhage on HF fluctuations while they prevented the postbleeding increase in MF oscillations. In conclusion, the present results show an association between the dependence of the postbleeding blood pressure level on catecholamines and the occurrence of slow fluctuations of BP. The buffering role of AVP suggests the establishment of a hierarchy between humoral systems in the genesis of the LF oscillations of BP, with the slow oscillations being generated by the main pressor system and being dampened by the other systems. The postbleeding rise in the MF component of SBP variability could be considered a reflection of the activations of both the sympathetic vasomotor drive and the RAS. The postbleeding increase in the HF component of BP variability was dampened by the activation of the humoral systems. These effects may reflect the low preload state due to hypovolemia.

Social isolation affects the pattern of cardiovascular responses to repetitive acoustic startle stimuli.

1. The aim of this study was to investigate the cardiovascular responses to repetitive alerting stimuli in rats subjected to intermittent social isolation, in comparison with animals housed in pairs. 2. Ten male Wistar rats were implanted with a blood pressure (BP) telemetric system and enrolled in a randomized cross-over study design. Rats were either isolated or housed in pairs for an 8 day period. At the end of each period, the animals were exposed to five acoustic stimuli (110 dB at 15 kHz, 80 ms after the impact, duration 700 ms) at 60 s intervals. For each stimulus, maximal BP and heart rate (HR) responses were calculated. BP variability was analysed in the frequency domain before the first stimulation using power spectral analysis. 3. Isolated animals showed more faster breathing (1.71 vs 1.42 Hz in the paired condition). The 0.4 Hz zone of the systolic BP spectral power was not significantly affected by isolation (1.11 vs 0.85 mmHg2). BP and HR resting levels of isolated rats (121 mmHg for the systolic BP and 290 b.p.m.) were similar to those of animals housed in pairs (119 mmHg for the systolic BP and 279 b.p.m.). 4. The first acoustic stimulus caused a brief rise in BP of a comparable amplitude in both conditions (24 +/- 2 mmHg). A biphasic HR response was also observed, but the delayed bradycardia was more marked during isolation (37 vs 6 b.p.m. decrease). BP and HR levels were restored within 20 s. 5. Interestingly, BP responses were progressively attenuated to become negligible at the fifth presentation (1 mmHg) in the isolated state, while during the paired state a substantial pressor response (13 mmHg) after each successive stimulus was maintained. Paired rats exhibited a constant HR profile across the trials, consisting in a slight HR increase (< 5 b.p.m.), concomitant with the BP elevation, followed by a delayed bradycardia (around 15 b.p.m.). HR profiles in the isolated condition differed markedly: HR rises increased in magnitude with the trial number, reaching 30 b.p.m. after the 5th trial. 6. Spontaneous BP and HR increases, as observed throughout the experiment were quantitatively small (6 mmHg and < 10 b.p.m.) in the two conditions. 7. These data indicate that isolation markedly affects the BP habituation profile to repetitive alerting stimuli. The BP response attenuation might unmask a tachycardic response. Alternatively, the amplified tachycardia following the latter stimuli might express sensitization to the conditioned fear resulting from isolation.

Contribution of humoral systems to the recovery of blood pressure following severe haemorrhage.

1. Profound haemorrhage activates a number of pressor mechanisms, including the release of catecholamines, angiotensin II and arginine-vasopressin, which contribute to the subsequent cardiovascular recovery. Using specific single or combined blockade with prazosin, losartan and Manning compound (AVPX), the aim of this study was to evaluate the involvement of the three pressor systems in blood pressure recovery following severe haemorrhage (20 ml kg-1). 2. Haemorrhage of conscious, unrestrained rats resulted in a significant initial decrease in blood pressure of approximately 60 mmHg, and heart rate of approximately 70 bpm. Then, blood pressure tended to return to the control level within 10 min. The total cardiovascular recovery corresponded to increments of 52 +/- 5 mmHg (81% of the acute fall) for systolic blood pressure, and of 92 +/- 22 bpm (124%) for heart rate at 60 min post-bleeding. Significant falls in haematocrit (-10.5 +/- 1.2%, P < 0.01), in plasma concentrations of proteins (-10.3 +/- 0.9 g l-1, P < 0.01) and haemoglobin (-2.58 +/- 0.72 g 100 ml-1, P < 0.05) were observed at 60 min post-bleeding. 3. Pretreatment with one or two specific antagonists did not exaggerate the initial fall in blood pressure. The initial bradycardia was weakened only by combined blockade with losartan and AVPX. 4. The blood pressure recovery from a haemorrhage was delayed by approximately 25 min by the inhibition of vasopressin activity. The systolic blood pressure recovery in control animals (81% of the acute fall) was blunted by losartan (55% of the acute fall), prazosin (49%), combined losartan and AVPX (36%), prazosin and AVPX (36%), and also by prazosin plus losartan (13%). The diastolic blood pressure recovery was blunted only in the groups where the activity of angiotensin II was inhibited by losartan. 5. In conclusion, we have shown that neither catecholamines, angiotensin II nor vasopressin, although activated, individually compensate the acute hypotensive response to haemorrhage. The contribution of vasopressin to the blood pressure recovery post-bleeding is transient and is rapidly replaced by the pressor activity of the catecholamines and angiotensin II. The full systolic blood pressure recovery from severe haemorrhage requires the combined activity of these two pressor systems, while the diastolic blood pressure recovery seems to be only dependent upon angiotensin II activity.

Contribution of the renin-angiotensin system to short-term blood pressure variability during blockade of nitric oxide synthesis in the rat.

1. The aim of this study was to investigate, by use of spectral analysis, (1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L-arginine analogue NG-nitro-L-arginine methyl ester (L-NAME); (2) the involvement of the renin-angiotensin system in these modifications, by use of the angiotensin II AT1-receptor antagonist losartan. 2. Blockade of NO synthesis was achieved by infusion for 1 h of a low-dose (10 micrograms kg-1 min-1, i.v., n = 10) and high-dose (100 micrograms kg-1 min-1, i.v., n = 10) of L-NAME. The same treatment was applied in two further groups (2 x n = 10) after a bolus dose of losartan (10 mg kg-1, i.v.). 3. Thirty minutes after the start of the infusion of low-dose L-NAME, systolic BP (SBP) increased (+10 +/- 3 mmHg, P < 0.01), with the effect being more pronounced 5 min after the end of L-NAME administration (+20 +/- 4 mmHg, P < 0.001). With high-dose L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg, P < 0.05) and reached a maximum after 40 min (+53 +/- 4 mmHg, P < 0.001); a bradycardia was observed (60 min: -44 +/- 13 beats min-1, P < 0.01). 4. Low-dose L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2, P < 0.05), whereas the high dose of L-NAME not only increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2, P < 0.001) but also decreased the mind frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, P < 0.05) of SBP. 5. Losartan did not modify BP levels but had a tachycardic effect (+45 beats min-1). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2, P < 0.001), prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose of L-NAME. Losartan also prevented the amplification of the LF oscillations of SBP induced by L-NAME; the decrease of the MF oscillations of SBP induced by L-NAME was reinforced after losartan. 6. We conclude that the renin-angiotensin system is involved in the increase in variability of SBP in the LF range which resulted from the withdrawal of the vasodilating influence of NO. We propose that NO may counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.

[Contribution of the renin-angiotensin system to the variability of blood pressure in hypertensive rat after blockade of nitric oxide synthesis]. / Contribution du système rénine-angiotensine à la variabilité tensionnelle du rat hypertendu après blocage de la synthèse du monoxyde d'azote.

The aim of this study was to investigate, using spectral analysis, 1) the blood pressure (BP) variability changes in the conscious rat during blockade of nitric oxide (NO) synthesis by the L-arginine analogue L-NAME; 2) the involvement of the renin-angiotensin system in these modifications, using the angiotensin II AT1-receptor antagonist losartan. The blockade of the NO synthesis was made by infusion for 1 hour of a low dose (10 micrograms/kg/min, i.v.; n = 10) and a high dose (100 micrograms/kg/min, i.v.; n = 10) of L-NAME. The same treatment was applied in two further groups (n = 2 x 10) after a bolus of losartan (10 mg/kg, i.v.). The low dose of L-NAME increased systolic BP (SBP) on and after thirty min of infusion (+10 +/- 3 mmHg; p < 0.01). BP reached a maximum value 5 min after stopping L-NAME administration (+20 +/- 4 mmHg; p < 0.001). With the high dose of L-NAME, SBP increased immediately (5 min: +8 +/- 2 mmHg; p < 0.05) and reached a maximum at 40 min (+53 +/- 4 mmHg; p < 0.001); a bradycardia was observed (60 min: -44 +/- 13 batt/min; p < 0.01). The low dose of L-NAME increased the low-frequency component (LF: 0.02-0.2 Hz) of SBP variability (50 min: 6.7 +/- 1.7 mmHg2 vs 3.4 +/- 0.5 mmHg2; p < 0.05). The high dose of L-NAME increased the LF component (40 min: 11.7 +/- 2 mmHg2 vs 2.7 +/- 0.5 mmHg2; p < 0.001) and decreased the mid frequency (MF: 0.2-0.6 Hz) component (60 min: 1.14 +/- 0.3 mmHg2 vs 1.7 +/- 0.1 mmHg2, p < 0.05) of SBP. Losartan did not modify BP levels but had a tachycardic effect (+33 +/- 10 batt/min; n = 27). Moreover, losartan increased MF oscillations of SBP (4.26 +/- 0.49 mmHg2 vs 2.43 +/- 0.25 mmHg2; p < 0.001; n = 27). Losartan prevented the BP rise provoked by the low-dose of L-NAME and delayed the BP rise provoked by the high-dose. Losartan prevented the amplification of the LF oscillations of SBP induced by the L-NAME; the decrease of the MF oscillations of SBP induced by the L-NAME was reinforced after losartan). We concluded that the renin-angiotensin system is involved in the increase of variability of SBP in the LF range which resulted from the withdrawal of the vasodilatating influence of NO. We proposed that NO could counterbalance LF oscillations provoked by the activity of the renin-angiotensin system.

Contribution of the renin-angiotensin and kallikrein-kinin systems to short-term variability of blood pressure in two-kidney, one-clip hypertensive rats.

Spectral analysis was recently chosen to characterize the fast oscillations, depending on the autonomic nervous system, in heart rate and blood pressure variabilities. Humoral stimuli could impinge on the low-frequency domain of blood pressure variability since the time lag to humoral system activation is greater. This study was designed to analyse low-frequency components of short-term variability of blood pressure of conscious rats in conditions where humoral systems were activated. We studied rats with two-kidney, one-clip Goldblatt hypertension in which the blood pressure level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and diastolic blood pressure and heart rate were computed in the high (respiratory)-, mid (0.2-0.6 Hz)- and low (0.02-0.2 Hz)-frequency bands, as detected by the fast Fourier transform technique in consecutive 102-s stationary periods. Hypertensive rats exhibited a marked low-frequency component of systolic (+261%) and diastolic (+169%) blood pressure variabilities when compared to sham-operated animals. First, losartan, a selective non-peptide angiotensin AT1 receptor antagonist, reduced this low-frequency component (-44% and -25% for systolic and diastolic blood pressure). In a second series of hypertensive rats, HOE 140, D-Arg-[Hyp3,Thi5,D-Tic7,Oic8]bradykinin, a bradykinin B2 receptor antagonist, decreased the low-frequency component of systolic (-28%) and diastolic (-40%) blood pressure. Losartan, added after HOE 140, induced a supplementary decrease of the low-frequency component (-60% and -42% for systolic and diastolic blood pressure). After the combined blockade, the low-frequency components of systolic and diastolic blood pressure variabilities of the hypertensive rats were equivalent to those of the control rats. Two-kidney, one-clip hypertension was also associated with an elevation of the mid-frequency component of the systolic blood pressure (+55%). The administration of HOE 140 did not change this component while losartan, alone or added after HOE 140, led to an increase (around +100%) in mid-frequency oscillations of systolic blood pressure. The high-frequency oscillations of systolic blood pressure were increased by losartan in the two series of hypertensive rats. Losartan increased the mid-frequency component of heart rate variability in sham-operated rats while the heart rate variability was not modified during any of the treatment periods in two-kidney, one-clip rats. In conclusion, an increase in the low-frequency component of blood pressure variability was observed in a model of hypertension where the blood pressure is dependent upon humoral activities. The reduction of the slow fluctuations following the combined blockade of the kallikrein-kinin and the renin-angiotensin systems suggested the contribution of these humoral systems to this low-frequency component of blood pressure variability.

Effects of graded hemorrhage on short-term variability of blood pressure in conscious rats.

A controlled graded bleeding was performed in conscious rats with 15 min intervals between two withdrawals, in order to induce a 25% blood loss without hypotension. Heart rate (HR) was unaffected as well. The spectral profiles of systolic blood pressure (SBP) analyzed on 51.2 s segments exhibited increases in the high frequency (HR, respiratory) component. This increase paralleled the blood loss with a rise ranging from 20% for a 1 mL/kg hemorrhage to 90% for a 11 mL/kg removal. These changes were associated with increases in the mid-frequency (MF, Mayer waves) component of SBP variability. These latter rises were between 30 and 40% of the control value. Breathing frequency (BF) and blood gases were unaltered following hemorrhage. A shift of fluid occurred during the 3 h session as reflected by the significant hemodilution. Rats were also bled after pretreatment with prazosin (1 mg/kg) or with an association of prazosin (1 mg/kg) and losartan (10 mg/kg). These treatments increased HR. A marked fall in SBP occurred with the double blockade. Hemorrhage determined a relative bradycardia together with the SBP decrease (reversible shock) after prazosin and losartan treatment. Prazosin determined opposite changes in MF (-33%) and HF (+58%) SBP components. A further decrease in the MF SBP component was observed following the double blockade. Spectral profiles following hemorrhage were unchanged compared to the prehemorrhage blocked levels. Therefore graded nonhypotensive, ie, normotensive hemorrhage in rats, was associated with progressive increases in the respiratory SBP variations, estimated from the SBP spectrum. This sensitive index could reflect the low preload state due to hypovolemia. The hemorrhage-induced MF SBP component increase could reflect an increased sympathetic vasomotor drive, prevented with prazosin, as a reflex adjustment to hypovolemia. Renin activation could also contribute to the genesis of MF waves and its role in maintaining BP following hemorrhage was exemplified with alpha 1-adrenoceptor blockade.

[Hormonal contribution to short-term variability of blood pressure in a renovascular hypertension model]. / Contribution hormonale à la variabilité tensionnelle dans un modèle d'hypertension réno-vasculaire.

Spectral analysis was recently chosen to characterize the fast oscillations depending on the autonomic nervous system. Humoral stimuli could impinge on low frequency (LF) domain of blood pressure (BP) since the time lag to humoral systems activation is larger. This study was designed to analyse LF components of short-term variability of BP of conscious rats in conditions where humoral systems were activated. We studied rats with two-kidney Goldblatt hypertension in which the BP level was dependent upon the renin-angiotensin and kallikrein-kinin systems. Spectral powers of the systolic and diastolic BP and heart rate (HR) were computed in the high (respiratory, HF), mid (0.2-0.6 Hz, MF) and low (0.02-0.2 Hz, LF) frequency bands, as detected by the Fast Fourier Transform technique on consecutive 102-s stationary periods. Renal hypertension by a two-kidney one clip procedure was associated with a marked rise in SBP (+47 mmHg) and no significant change in HR. Renal hypertension selectively increased the LF component of SBP (+86%) when hypertensive rats were compared to sham operated animals. First, administration of losartan, a selective nonpeptide angiotensin II receptor antagonist, to sham rats resulted in a moderate SBP decrease, a significant tachycardia (+47 batt/min) with no change in BP and HR spectra profiles. Losartan determined in the hypertensive group a marked fall in SBP (-25 mmHg) with a significant tachycardia (+50 batt/min). Interestingly, losartan reduced the LF component of SBP (-26%). In a second series of normotensive and hypertensive rats, Hoe 140, a bradykinin B-2 receptor antagonist, did not affect the BP and HR levels of the two groups of rats. Hoe 140 decreased the LF component of SBP variability (-28%). Losartan, added after Hoe 140, decreased the BP (-17 mmHg) in association with a tachycardia (+59 batt/min) and induced a supplementary decrease of the LF component of SBP variability (-60%) in hypertensive rats. After the combined blockade, the LF component of SBP of the hypertensive rats was equivalent to that of the sham rats. Thus, an increase in the LF component of BP variability was observed in a model of hypertension where the BP is dependent upon humoral factors. The contribution of the renin-angiotensin and kallikrein-kinin systems in the slow fluctuations of BP was demonstrated using two specific antagonists losartan and Hoe 140.

Effects of bradykinin on short-term variability in blood pressure and heart rate in rats: a spectral study.

Using a spectral procedure, we studied the effects of two treatment regimens of bradykinin (BK) on the blood pressure (BP) and heart rate (HR) variabilities in conscious Wistar rats. We performed a second series of experiments with hydralazine, at doses equihypotensive to those used in BK treatments, to discriminate between a specific effect of the peptide and those induced by vasodilation. We assessed the activity of the sympathetic nervous system (SNS), using the responses to atenolol and prazosin. First, at a subhypotensive treatment regimen, BK (5 micrograms/min) increased low-frequency (LF, 0.02-0.2 Hz) and mid-frequency (MF, 0.2-0.6 Hz) frequency components of BP variability and also activated the SNS. Lesser enhancements of LF and MF areas were induced by hydralazine (0.15 mg/kg). Second, high-dose treatment regimens of BK (100 micrograms/min) and hydralazine (2 mg/kg), which markedly decreased BP, did not change the areas of the LF and MF components of BP variability, whereas overactivity of the SNS was still assessed with the adrenergic blockers. On the other hand, high-dose BK induced a sixfold increase in the amplitude of the high frequency (HF, respiratory) component of BP. The effect of bradykinin on HF domain was associated with an increase in the depth of respiration in a group of anesthetized rats. Hoe 140 (60 micrograms/kg), a B-2 BK-receptor antagonist, abolished both the effects of BK on HF fluctuations in BP and the effects on breathing pattern. Our results demonstrate that BK induced different effects on LF and MF fluctuations in BP depending on the treatment regimen, whereas the SNS was activated by the two selected treatment regimens. Therefore, the MF component of BP variability should be considered only as a marker of the activity of the SNS when the BP level was not affected. Furthermore, we characterized an amplifying effect of BK on the HF domain of BP variability partly mediated by an increase in the depth of respiration.