Sympathectomy inhibits the vasoactive effects of nicotine in conscious rats.

OBJECTIVE: The mechanisms underlying the pressor response to nicotine are incompletely understood. Although sympatho-adrenergic activation plays a major role, the relative contribution of adrenal vs. neurally released catecholamines and the possible role of non-adrenergic factors (e.g. vasopressin release) is not established. METHODS: We examined the cardiovascular responses to graded i.v. injections of nicotine (1 to 100 micrograms kg-1) in conscious Wistar-Kyoto rats under control conditions and (i) after chemical sympathectomy by 6-hydroxydopamine, which destroys sympathetic endings but spares the adrenal medulla; (ii) after an alpha-adrenergic blockade by phenoxybenzamine; (iii) after a V1 vasopressin receptor blockade by a specific antagonist. RESULTS: In control rats, nicotine caused a dose-dependent tachycardiac and pressor response. Both responses were abolished by sympathectomy, whereas the alpha-blockade left the tachycardiac response unaffected but inhibited the pressor response: the V1 vasopressin receptor blockade had no effect on either the tachycardiac or pressor response. CONCLUSIONS: We conclude that in the conscious rat; (1) the pressor response to nicotine mainly depends on peripheral alpha-adrenergically-mediated vasoconstriction; (2) the vasomotor effect is caused by neural rather than adrenomedullary catecholamine release; (3) the nicotine-induced increase in heart rate (and presumably cardiac output) is per se unable to raise blood pressure, and (4) the nicotine-induced release of vasopressin plays no significant role in the pressor response.

Endothelin and mechanical properties of the carotid artery in Wistar-Kyoto and spontaneously hypertensive rats.

The aim of this study is to evaluate the role of endothelin in the control of the static mechanical properties of in vitro carotid arteries from 14-week-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). An in vitro preparation in which the artery was allowed to longitudinally elongate similarly to the in situ carotid artery was employed. The diameter of in vitro carotid arteries subjected to static pressures (from 25 to 200 mmHg in 25 mmHg steps) was determined by videomicroscopy and computer-assisted image analysis, the cross-sectional compliance- and distensibility-pressure curves being then derived. The role of endothelin was assessed by incubating carotid arteries with the selective ETA and ETB endothelin receptor antagonists BQ123 and BQ788, respectively. These effects were compared with those observed under control conditions, as well as with those following complete abolition of vascular smooth muscle tone by potassium cyanide (KCN). Carotid diameter was significantly larger, and compliance and distensibility significantly smaller, in SHR compared to WKY rats. Local incubation with BQ123 was associated with significant dilations as well as significant increases in cross-sectional compliance and distensibility in both strains. This was even more pronounced with KCN, while BQ788 had no effect. The results of the present study suggest that: (i) endothelin exerts a tonic stiffening effect on the in vitro common carotid artery; (ii) this effect is mediated via the ETA endothelin receptor, and (iii) the stiffening effect of endothelin is exerted to a similar extent in the carotid arteries of normotensive WKY and SHR rats.

Effects of altering the interval between the stimulus and the reflex response in the analysis of the baroreceptor control of the sinus and atrioventricular nodes in man.

Baroreceptor control of the sinus node may be determined by raising or lowering blood pressure with intravenous bolus injections of phenylephrine or glyceryl trinitrate and calculating the slope of the linear regression between the drug induced changes in systolic blood pressure and RR interval using shift 1 coupling--namely, coupling of each systolic blood pressure value with the interval of the following cardiac cycle. To assess whether shift 1 coupling provides the best linear fit and the highest regression slope nine subjects received phenylephrine and glyceryl trinitrate injections both during spontaneous sinus rhythm and during atrial pacing to evaluate baroreflex control of the sinus and of the atrioventricular node respectively. In regression analysis of the data, for each drug injection nine different shifts (from 0 to 8) were used to couple systolic blood pressure with RR or StQ intervals. When the mean results from all subjects were compared the use of shift 1 was equal or superior to the use of any other shift for both the RR and the StQ interval responses evoked by either phenylephrine or glyceryl trinitrate. In many instances, however, the shift that provided the highest correlation and regression coefficient was different from shift 1, and the use of these best individual shifts provided results considerably different from those obtained with the standard shift 1. It is concluded that in the regression analysis of baroreflex cardiac responses to vasoactive drugs the regular use of shift 1 does not invariably provide the best estimation of baroreflex sensitivity. This is better achieved by calculating the best shift in individual responses.

Sensitization of aortic baroreceptors by high salt diet in Dahl salt-resistant rats.

High salt diet alters neural cardiovascular control. This influence has been attributed to central neural or efferent mechanisms. To test the hypothesis that a high salt diet might alter afferent baroreceptor function, Dahl salt-resistant (DR) and salt-sensitive rats (DS) were fed a high or a low salt diet. Blood pressure was measured intra-arterially in unanesthetized animals. Aortic baroreceptor function was then evaluated during urethane anesthesia by recording multifiber aortic depressor nerve activity during a phenylephrine-induced blood pressure ramp. Mean arterial pressure in the conscious state was elevated (155 +/- 5 [SE]mm Hg) in DS fed a high salt diet but was normal in DS fed a low salt diet and in DR. Slopes of linear regressions relating aortic nerve discharge to mean arterial pressure were 71% higher in DR fed a high salt diet than in DR fed a low salt diet (p less than 0.025), indicating that high salt potentiated baroreceptor function in DR. In contrast, high salt diet produced no significant effects on baroreceptor function in DS. No salt-induced changes in dynamic or static aortic distensibility (assessed from pressure-volume curves of the in situ isolated arch) were detectable in either rat strain. Absence of salt-induced baroreceptor sensitization in DS was not due to the hypertensive state because the sensitization also failed to occur in separate groups of DS in which salt-induced hypertension had been prevented by chemical sympathectomy with 6-OH-dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation of the baroreceptor-heart rate reflex by sympathectomy in conscious rats.

In both animals and humans, stimuli leading to sympathetic activation are accompanied by an impairment of the baroreceptor-heart rate reflex. To determine whether sympathetic activity normally interferes with this reflex function we examined in conscious Wistar-Kyoto (WKY) rats the effect of chemical sympathectomy by 6-hydroxydopamine on the bradycardic response to baroreceptor stimulation induced by raising blood pressure via intravenous phenylephrine boluses; control rats received vehicle. Spontaneously hypertensive rats were also studied because in these animals there is both a baroreceptor reflex impairment and a sympathetic overactivity. Baroreceptor reflex sensitivity, calculated as the ratio of the peak increase in pulse interval to the peak increase in mean arterial pressure, was 75% greater in sympathectomized WKY rats than in control WKY rats (1.28 +/- 0.15 versus 0.73 +/- 0.10 msec/mm Hg, mean +/- SEM; p less than 0.01). The sympathectomy-induced increase in sensitivity was even larger in spontaneously hypertensive rats (SHR) (1.26 +/- 0.12 versus 0.44 +/- 0.06 msec/mm Hg in sympathectomized SHR versus control SHR, +186%; p less than 0.01) so that the impaired baroreceptor reflex sensitivity observed in control SHR as compared with control WKY rats (-40%, p less than 0.01) was no longer detectable in the sympathectomized groups. To establish whether the sympathectomy-induced potentiation of the reflex was due to an increase in cardiac responsiveness to vagal stimuli, we subjected separate groups of anesthetized, vagotomized SHR and WKY rats to graded electrical stimulation of the right efferent vagus. The bradycardic effects of vagal stimulation, however, were similar in sympathectomized and control animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Inverse relationship between heart rate and blood pressure variabilities in rats.

The interplay of heart rate variability, baroreceptor control of heart rate, and blood pressure (BP) variability was examined in chronically instrumented, unanesthetized, freely moving rats in which the efferent neural influences on heart rate were pharmacologically altered. In each rat, BP was recorded continuously for 90 minutes in the control condition and in one or more of the following conditions: 1) beta-adrenergic receptor blockade by propranolol, 1 mg/kg; 2) cholinergic blockade by atropine, 0.75 mg/kg, and 3) combined blockade by propranolol plus atropine. Each BP recording was analyzed beat-to-beat by a computer that calculated heart rate and BP variabilities, both expressed as variation coefficients. In addition, under each condition the sensitivity of the arterial baroreceptor control of heart rate was assessed by measuring the reflex changes in pulse interval in response to BP changes induced by bolus i.v. injections of phenylephrine and nitroprusside. As compared with the control condition, 1) propranolol (n = 10) reduced heart rate variability by 23 +/- 4% (p less than 0.01), only slightly impaired baroreceptor reflex sensitivity, and did not significantly modify BP variability (+11 +/- 7%); 2) atropine (n = 11) reduced heart rate variability by 30 +/- 7% (p less than 0.01), drastically impaired baroreceptor reflex sensitivity, and increased BP variability (+40 +/- 8%, p less than 0.01); 3) combined blockade (n = 10) caused variability and baroreceptor reflex changes similar to those induced by atropine alone. Thus, heart rate variability depends on both vagal and sympathetic influences. However, only the former component affects BP variability, that is, it plays an antioscillatory role.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric oxide dependent vasodilation in young spontaneously hypertensive rats.

Conflicting evidence exists on the possible impairment of tonic nitric oxide (NO) mediated vasodilation as a causative factor in the genesis of human as well as experimental hypertension. We evaluated the tonic NO-dependent vasodilation from the pressor response to NO synthesis inhibition by NG-monomethyl-L-arginine (L-NMMA) in 9 conscious, chronically instrumented spontaneously hypertensive rats (SHR) at 12 weeks of age, ie, during the early established hypertensive stage. Nine age-matched Wistar-Kyoto rats (WKY) were used as controls. The pressor responses to L-NMMA (100 mg . kg-1 IV bolus plus 1.5 mg . kg-1 . min-1 infusion for 60 minutes) as well as to non NO-dependent pressor stimuli, namely, vasopressin (2, 4, and 8 ng . kg-1) and phenylephrine (0.5, 1, and 2 microg . kg-1) given as IV boluses, were assessed both under control conditions and during suppression of autonomic reflexes by hexamethonium (30 mg . kg-1 IV bolus+1.5 mg . kg-1 . min-1 infusion). Rather than being reduced, the pressor responses to L-NMMA were 39% and 71% larger in the control and areflexic conditions, respectively, than those observed in WKY (both P<0.01). A similar pattern was observed for the pressor responses to vasopressin (+37% and +68% in the control and areflexic conditions, respectively; both P<0.01) and phenylephrine, (+20% and +52%; both P<0.05). Additional groups of 6-week-old prehypertensive SHR (n=11) and age-matched WKY (n=11) were subjected to an identical protocol: in these animals, the pressor responses to L-NMMA were similar in each strain, as were the pressor responses to vasopressin and phenylephrine in both control and areflexic conditions. In conclusion, our observations indicate that during the developmental phase of hypertension in the SHR model, namely, during the prehypertensive as well as the early established hypertensive stage, NO-dependent vasodilation is preserved (if not enhanced) so that a putative impairment of this function provides no significant pathogenic contribution to the onset of hypertension in this experimental model.

Atrial natriuretic factor and arterial baroreceptor reflexes in unanesthetized rats.

The modulation exerted by atrial natriuretic factor (ANF) on the cardiac and vascular influences of arterial baroreceptors was investigated in two groups of unanesthetized, chronically instrumented normotensive rats. In group 1, the reflex control of heart rate was assessed by graded baroreceptor stimulations and deactivations obtained by intravenous boluses of phenylephrine and nitroprusside. Under either circumstance, baroreceptor reflex sensitivity was expressed as the linear regression slope relating the chronotropic responses to the drug-induced mean arterial pressure changes. In group 2, right common carotid occlusion was performed in rats with their aortic and left carotid sinus baroreceptors denervated to assess the baroreceptor control of blood pressure; the reflex response was quantitated as the peak blood pressure rise observed during the maneuver. The reflex studies were performed before and during atriopeptin III infusion (0.15-0.20 micrograms/kg/min for 60 minutes). ANF augmented the bradycardic response to phenylephrine by 102.5 +/- 29% (p less than 0.01), reduced the tachycardic response to nitroprusside by 67.7 +/- 6.4% (p less than 0.01), and failed to modify the pressor response to carotid occlusion (-6.8 +/- 2.1%, p = NS). In a separate group of rats infused with low dose nitroprusside, no change in the baroreceptor-heart rate reflex was observed. ANF infusion (0.20 micrograms/kg/min) performed in further separate groups of conscious rats raised plasma ANF to 480 +/- 58 fmol/ml. Values in control vehicle-infused rats were 50 +/- 8 fmol/ml. Vascular reactivity (pressor response to intravenous phenylephrine boluses in anesthetized, sinoaortic-denervated rats) was only minimally reduced by ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac parasympathetic hyperresponsiveness in spontaneously hypertensive rats.

The bradycardic response to baroreceptor stimulation is impaired in human and experimental hypertension. Because this bradycardia mainly depends on the vagus, this may reflect a reduced cardiac parasympathetic responsiveness, which would parallel the reduced cardiac adrenergic responsiveness observed in hypertension. To test this hypothesis, 12-week-old spontaneously hypertensive rats (n = 12) and normotensive Wistar-Kyoto rats (n = 11) were anesthetized with ketamine and underwent bilateral vagotomy. Cardiac parasympathetic responsiveness was assessed from the bradycardia induced by 1) graded electrical stimulation of the right efferent vagus (1-16 Hz) and 2) graded intravenous injections of methacholine (1-8 micrograms.kg-1). The slope of the linear regression between the bradycardiac response and the applied stimulus was taken as the measure of cardiac parasympathetic responsiveness. To identify the onset of possible alterations in cardiac parasympathetic responsiveness in hypertension, the study was extended to younger (8-week-old) spontaneously hypertensive (n = 11) and Wistar-Kyoto (n = 13) rats. With vagal stimulation, cardiac parasympathetic responsiveness was greater in 12-week-old spontaneously hypertensive rats than in 12-week-old Wistar-Kyoto rats (24.8 +/- 5.4 versus 10.1 +/- 1.2 beats per minute per hertz, mean +/- SEM, p less than 0.035). This was also the case with methacholine (18.8 +/- 3.5 versus 13.1 +/- 4.4 beats per minute per microgram per kilogram, p less than 0.045). In contrast, cardiac parasympathetic responsiveness was similar, with both vagal stimulation and methacholine, when tested in the younger spontaneously hypertensive and Wistar-Kyoto groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathectomy and cardiovascular spectral components in conscious normotensive rats.

We examined the extent to which sympathetic influences are reflected by spectral powers of blood pressure and pulse interval in specific frequency bands in spontaneously behaving Wistar-Kyoto rats subjected to continuous intraarterial blood pressure recording. The rats were pretreated with 6-hydroxydopamine (150 mg/kg twice in 1 week, n = 19) to produce chemical sympathectomy or received vehicle (n = 15). In the sympathectomized group, additional monitoring sessions were performed with rats under alpha-adrenergic receptor blockade with phenoxybenzamine (n = 8), beta-receptor blockade with propranolol (n = 7), or cholinergic receptor blockade with atropine (n = 8). Blood pressure signals were analyzed by a computer to calculate spectral powers (fast Fourier transform) in the low-frequency (0.025 to 0.1 Hz), mid-frequency (0.1 to 0.6 Hz), and high-frequency (0.8 to 3.0 Hz) bands. In sympathectomized rats, low-frequency power of blood pressure was 70% greater than in intact rats, whereas mid-frequency power was 60% smaller (P < .05 for both) and high-frequency power was unchanged. High-frequency power of pulse interval was also unchanged in sympathectomized rats, whereas low- and mid-frequency powers were reduced by approximately 50% (P < .05). No further alterations in spectral powers were observed by adding alpha- or beta-adrenergic blockade to sympathectomy, whereas adding cholinergic blockade caused a striking reduction in all pulse interval powers. Thus, mid-frequency blood pressure power depends on sympathetic but also to a substantial extent on nonsympathetic influences. Sympathetic influences do not contribute to low-frequency blood pressure power, having instead a restraining effect. The low- and mid-frequency pulse interval powers depend on both sympathetic and vagal influences. Thus, no blood pressure or pulse interval power in the mid- and low-frequency ranges can be regarded as a specific marker of sympathetic activity.

Effect of sympathectomy on mechanical properties of common carotid and femoral arteries.

Sympathetic stimulation is accompanied by a reduction of arterial distensibility, but whether and to what extent elastic and muscle-type arterial mechanics is under tonic sympathetic restraint is not known. We addressed this issue by measuring, in the anesthetized rat, the diameters of the common carotid and femoral arteries with an echo-Doppler device (NIUS 01). Blood pressure was measured by a catheter inserted contralaterally and symmetrically to the vessel where the diameter was measured. Arterial distensibility over the systolic-diastolic pressure range was calculated according to the Langewouters formula. Data were collected in 10 intact (vehicle pretreatment) and 9 sympathectomized (6-hydroxydopamine pretreatment) 3-month-old Wistar-Kyoto rats. Compared with the intact animals, sympathectomized rats showed a marked increase in arterial distensibility over the entire systolic-diastolic pressure range. When quantified by the area under the distensibility-pressure curve, the increase was 59% and 62% for the common carotid and femoral arteries, respectively (P<.01 for both). In the femoral but not in the common carotid artery, sympathectomy was accompanied also by an increase in arterial diameter (+18%, P<.05 versus intact). Therefore, in the anesthetized normotensive rat, sympathetic activity exerts a tonic restraint on large-artery distensibility. This restraint is pronounced in elastic vessels and even more pronounced in muscle-type vessels.

Heart rate-dependent stiffening of large arteries in intact and sympathectomized rats.

In the anesthetized rat, acute increases in heart rate are accompanied by a reduction in arterial distensibility, which is a significant phenomenon in elastic-type vessels such as the common carotid but much less evident in muscle-type vessels such as the femoral artery. Because the sympathetic nervous system importantly reduces arterial distensibility, the present study aimed to determine whether sympathetic influences (1) are involved in the heart rate-dependent changes in arterial distensibility and (2) exert differential effects on elastic-type versus muscle-type arteries. To address this issue, 9 sympathectomized (6-hydroxydopamine) and 10 vehicle-treated, 12-week-old, pentobarbitone-anesthetized Wistar-Kyoto rats were subjected to atrial pacing via a transjugular catheter at 5 different randomly sequenced rates (280, 310, 340, 370, and 400 bpm). After each step, spontaneous sinus rhythm was allowed to return to normal. Common carotid and femoral artery diameters were measured by an echo Doppler device (NIUS 01), and blood pressure was measured via catheter inserted into the contralateral vessel. Arterial distensibility was calculated over the systolic-diastolic pressure range according to the Langewouters formula. In the common carotid artery, progressive increases in heart rate determined progressive and marked reductions of distensibility (range, 15% to 43%) in sympathectomized and intact rats. In the femoral artery, the stiffening effect of tachycardia was present in sympathectomized rats (range, 21% to 42%), at variance with the inconsistent changes observed in intact rats. In conclusion, our experiments support the notions (1) that in predominantly elastic-type arteries, the stiffening effect of tachycardia is exerted independently of sympathetic modulation of the vessel wall properties and (2) that in predominantly muscle-type arteries, removal of sympathetic influences unmasks the stiffening effect of tachycardia.

Intra-arterial pressure alterations during tail-cuff blood pressure measurements in normotensive and hypertensive rats.

The heating and restraint inherent to tail-cuff measurement of systolic blood pressure (SBP) in rats may alter SBP and introduce a 'biological' error in its estimation by this technique. This problem was examined in unanesthetized normotensive and hypertensive rats fitted with an arterial catheter. All SBP values recorded in unrestrained rats during a 2 h period were averaged by computer and compared with intra-arterial SBP measurements observed while the rat was being subjected to the tail-cuff procedure. With the latter procedure, SBP was 16 +/- 2 mmHg lower in normotensive rats (P less than 0.001) and 7 +/- 3 mmHg higher in hypertensive rats (P less than 0.05) than when the rats were unrestrained. The effects of heat and restraint, both separately and in combination, on SBP were evaluated during four additional 30-min monitoring periods. In both groups of rats, restraint failed to alter SBP and heat lowered it slightly. The two stimuli, combined, lowered SBP in normotensive rats, but raised it by 12 +/- 2 mmHg in hypertensive rats (P less than 0.01). Thus, tail-cuff SBP measurements represent under- and overestimates in normotensive and hypertensive rats, respectively, since the two groups respond to the procedure in opposite manners.

Differential effects of aging on the heart rate and blood pressure influences of arterial baroreceptors in awake rats.

The effect of aging on arterial baroreceptor control of heart rate and blood pressure was evaluated in unanesthetized normotensive rats aged 5-6 (young), 12-16 (adult) and 75-90 (old) weeks. Each rat was chronically implanted with arterial and venous femoral catheters and with bilateral balloon-in-cuff occluders around the common carotid arteries. Baroreceptor control of heart rate was assessed by the bradycardic and tachycardic response to intravenous boluses of phenylephrine and nitroprusside, respectively. Carotid baroreceptor control of blood pressure was assessed by a 12-s bilateral common carotid occlusion (CCO). All baroreflex responses were similar in young and adult rats. Compared with the young group, old rats showed a marked reduction of the bradycardic and tachycardic baroreflex response (-42% and -46%, respectively, P less than 0.05). The initial pressor responses to CCO were also impaired in the old animals (3 s: -63%, 6 s: -54%; both P less than 0.01), whereas the peak pressor response (9 and 12 s) was virtually identical in the young and old groups. The preservation of the peak pressor response to CCO in old rats was independent of chemoreceptor activation, aortic baroreceptors or cerebral ischemia. Thus, aging impairs baroreceptor control of heart rate but alters baroreceptor control of blood pressure, as assessed by the pressor response to CCO, only in its fast-developing component, leaving its longer-term component unaffected.

Sympathetic, parasympathetic and non-autonomic contributions to cardiovascular spectral powers in unanesthetized spontaneously hypertensive rats.

OBJECTIVE: To determine whether spectral powers of blood pressure and pulse interval can specifically reflect sympathetic and parasympathetic effects in unanesthetized, free-moving spontaneously hypertensive rats (SHR). DESIGN: Spectral powers were observed before and after various autonomic interventions in chronically instrumented rats. MATERIALS AND METHODS: Chemical sympathectomy was produced in 12-week-old SHR by repeated injections of 6-hydroxydopamine, while control rats were given vehicle alone. Chronic arterial and venous catheters were inserted in the femoral artery and vein. Blood pressure was recorded beat-to-beat for 90 min in free-moving rats; further recording sessions were obtained under additional alpha-receptor blockade with phenoxybenzamine at 1 mg/kg and/or additional cholinergic blockade with atropine at 0.8 mg/kg. Off-line computer analysis (fast Fourier transform) provided estimates of low- (0.025-0.1 Hz), mid- (0.1-0.6 Hz) and high-frequency (0.8-3.0 Hz) powers for blood pressure and pulse interval over consecutive periods of 100 s. RESULTS: The most noticeable findings were that sympathectomy produced a striking increase in the low-frequency power of blood pressure and a tendency (borderline statistical significance) to reduce the mid-frequency power of blood pressure. Additional alpha-receptor blockade had no effect on any spectral power whereas additional cholinergic blockade caused a further increase in the low-frequency blood pressure power and a drastic reduction in all pulse interval powers. CONCLUSIONS: In the unanesthetized SHR, sympathetic activity opposes low-frequency and marginally promotes mid-frequency blood pressure fluctuations; the pulse interval spectral expression of vagal effects is spread throughout the range of frequencies explored and is not confined to the high-frequency band. These data indicate that in SHR no spectral power can specifically reflect the effects of either autonomic limb.

Reproducibility of ultrasound assessment of common carotid and femoral artery compliance and distensibility in the anesthetized rat.

OBJECTIVE: To validate ultrasound assessment of common carotid and femoral artery compliance and distensibility in the anesthetized rat. MATERIALS AND METHODS: A reproducibility study was performed by taking measurements twice on two different days in anesthetized Wistar-Kyoto (WKY) rats. The common carotid or femoral arterial diameter on one side and the contralateral arterial blood pressure were measured using a 10-MHz probe echo-Doppler device and an arterial catheter, respectively. The pressure and diameter data were stored in a computer programmed to calculate the arterial compliance and distensibility coefficients (Reneman formulas) and compliance and distensibility indices (arctangent model of Langewouters). A second experimental session was repeated 1 day later, and mean values, day-to-day mean differences and repeatability coefficients were calculated for each parameter. RESULTS: For both the common carotid and the femoral artery, the mean values for heart rate, mean arterial pressure, arterial diameter, arterial compliance and arterial distensibility were similar on the first and second days; mean day-to-day differences were small and repeatability coefficients were in the range 5-10% of the mean value for diameter and mean arterial pressure and 10-20% of the mean value for compliance and distensibility. CONCLUSIONS: In the anesthetized rat, ultrasound evaluation of the mechanical properties of the common carotid and femoral arteries is a reliable and reproducible technique.

Heart rate-dependence of arterial distensibility in vivo.

OBJECTIVES: Viscous and inertial components contribute to arterial distensibility and compliance in vitro. The purpose of our study was to determine whether this phenomenon is of relevance in vivo, namely, whether arterial compliance is altered by an increase in heart rate. DESIGN: Arterial diameter was assessed by an echo-Doppler device in a common carotid and femoral artery, namely, in a large elastic and a muscle artery. The studies were performed in 12-week-old pentobarbitone-anaesthetized Wistar-Kyoto rats subjected to atrial pacing via a transjugular unipolar catheter at five different randomly sequenced rates (280, 310, 340, 370 and 400 beats/min). After each stage, spontaneous sinus rhythm was allowed to return. Blood pressure was measured via a catheter inserted into the carotid or femoral artery contralateral to the vessels in which the diameter was measured. Arterial compliance and distensibility values were derived according to the Langewouters formula. RESULTS: A progressive increase in heart rate caused by pacing was accompanied by progressive and marked reductions in carotid artery compliance and distensibility. When quantified by the area under the distensibility-pressure or compliance-pressure curve the reduction was in the range 15-43%. Although a tendency to a similar phenomenon was observed in the femoral artery, in the latter vessel the reduction in distensibility and compliance was less marked and statistically insignificant. CONCLUSIONS: In the anaesthetized rat acute increases in heart rate are accompanied by reductions in arterial compliance and distensibility. The effect is greater in elastic than in muscle arteries.

Lack of autonomic contributions to tonic nitric oxide-mediated vasodilatation in unanesthetized free-moving rats.

OBJECTIVE: To clarify the controversial issue of whether autonomic influences modulate vascular nitric oxide-mediated vasodilatation or even directly contribute to production of nitric oxide (NO) via nitroxidergic fibers. METHODS: Chronic venous and arterial catheters were implanted in Wistar-Kyoto rats (n = 65) for continuous blood pressure measurement, drug administration and blood sampling. Tonic NO-dependent vasodilatation in the conscious free-moving animal was evaluated as the pressor response to inhibition of NO synthesis by intravenous L-monomethylarginine (a 100 mg/kg intravenous bolus plus 0.5 mg/kg per min infusion for 30 min). Experiments were performed under control conditions, chemical sympathectomy by 6-hydroxy-dopamine, ganglionic blockade by hexamethonium, and surgical denervation of sino-aortic baroreceptors. RESULTS: Baseline mean arterial pressure was 100+/-4 mmHg (mean +/- SEM) in control rats and 73+/-3, 62+/-5, and 105+/-10 mmHg in sympathectomized, ganglion-blocked, and denervated rats, respectively. The peak increase in mean arterial pressure after administration of L-monomethylarginine was 38+/-3 mmHg in control rats and 51+/-3, 50+/-6, and 63+/-10 mmHg in sympathectomized, ganglion-blocked, and denervated rats, respectively. Epinephrine and norepinephrine levels in rats of separate groups of unanesthetized control, sympathectomized and ganglion-blocked animals were measured by high-performance liquid chromatography from an arterial blood sample, the results indicating drastic reductions in levels of both catecholamines in the ganglion-blocked (but not in the sympathectomized) rats compared with those in the control rats. CONCLUSIONS: Tonic NO-dependent vasodilatation can normally be maintained in the unanesthetized unrestrained rat irrespective of autonomic or humoral adrenergic influences.

Differential alterations of common carotid and femoral artery distensibility in 12-week-old spontaneously hypertensive rats.

OBJECTIVE: In essential hypertension, the mechanical properties of the radial artery have been shown to be largely unaltered, whereas more controversial and less reliable data have been obtained for the common carotid artery. We therefore examined the distensibility/pressure relationships of the predominantly elastic common carotid artery and of the predominantly muscle-type femoral artery in 12-week-old normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). METHODS: Eleven 12-week-old SHR and 10 age-matched WKY rats were anesthetized with sodium pentobarbitone. Blood pressure and pulse rate were measured by catheters inserted in the common carotid and in the femoral arteries, while contralateral arterial diameter was continuously recorded via an echo-tracking device. Arterial compliance was derived according to the Langewouters formula, and its values were normalized for the diameter, to obtain distensibility/pressure curves and to calculate the distensibility index. The Peterson elastic modulus was also calculated in order to obtain a pressure-independent estimate of arterial mechanical properties. RESULTS: Femoral artery distensibility/pressure curves and distensibility index were similar in the two groups of rats, the latter being 1.13+/-0.13 mm/mmHg10(-3) in SHR and 1.28+/-0.15 mm/mmHg10(-3) in WKY rats (means+/-SEM; NS). In contrast, in SHR, common carotid artery mechanical properties were clearly impaired, as shown by a marked reduction in distensibility index (2.55+/-0.16 mm/mmHg10(-3) in SHR versus 3.4+/-0.3 mm/mmHg10(-3) in WKY rats; P< 0.05), and by a significant increase in the Peterson elastic modulus. CONCLUSIONS: In the SHR model, high blood pressure alters the mechanics of large arteries even in the relatively early stage of the disease; however, the alterations are not homogeneous inasmuch elastic-type vessels are affected to a much greater extent than muscle-type vessels.

Spontaneous variability of regional haemodynamics in unanaesthetized rats.

AIM: To study the spontaneous variability in regional haemodynamics. METHODS: Twenty normotensive Wistar-Kyoto rats were chronically instrumented with an arterial catheter and with pulsed Doppler flowmeters on the distal aorta, and the superior mesenteric and left renal arteries. After surgical recovery, the rats were monitored in unrestrained conditions. The recorded signals were analysed beat-to-beat to obtain means and coefficients of variation for mean arterial pressure, heart rate, regional blood flow velocity (consecutive 0.8-s periods) and indices of regional vascular resistance (0.8-s ratio of mean arterial pressure to mean blood flow velocity). RESULTS: Muscle and splanchnic blood flow velocities were markedly variable, with coefficients of variation of 12.8 +/- 0.8 and 12.2 +/- 1.7% (means +/- SEM), respectively, about twice as large as the coefficient of variation for mean arterial pressure (6.2 +/- 0.3%). The renal blood flow velocity was slightly less variable than the muscle and splanchnic blood flow velocities, with a coefficient of variation of 10.4 +/- 0.8%, but still markedly and significantly more variable than systemic arterial pressure. A contingency analysis of paired variations in any two given parameters (arterial blood pressure, heart rate, blood flow velocities and indices of vascular resistance) showed a concordant pattern, the only exception being a distinctly discordant trend for the covariations in muscle and splanchnic blood flow velocities. CONCLUSIONS: Regional blood flow velocity and vascular resistance have a larger degree of spontaneous variability than systemic arterial pressure. Renal blood flow velocity is also highly variable, suggesting that short-term stimuli that affect the renal blood vessels are not countered by autoregulation to any great degree. We conclude that while central factors may drive concordant regional haemodynamic variations, some opposing changes in regional blood flow velocity may cancel each other out, thereby reducing the variability in systemic blood pressure.