Effects of phencyclidine and ketamine on cardiovascular activity and temperature in the squirrel monkey

Heart rate (HR), mean arterial blood pressure (BP) and core temperature (TEMP) were recorded from chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous (i.v.) injections of phencyclidine and ketamine and intramuscular (i.m.) injections of ketamine. Phencyclidine (0.03-3.0 mg/kg) and ketamine (0.3-30.0 mg/kg) i.v. increased BP and decreased TEMP, and the changes in BP and in TEMP were greater in magnitude and duration after phencyclidine. Heart rate also increased monotonically after 0.03-0.3 mg/kg phencyclidine or 0.3-10.0 mg/kg ketamine, but the effects of higher doses of either drug were biphasic with decreases followed by increases in HR. When either of two doses of ketamine (10.0 and 30.0 mg/kg) was injected i.m., the effects were qualitatively similar to those observed after i.v. administration although of much less magnitude, and there was no evidence of a biphasic change in HR. The data show that these two dissociative anesthetics differ in duration of action and in magnitude of effect on cardiovascular activity and core temperature in the squirrel monkey, and that phencyclidine is approximately ten times as potent as ketamine.     

Cardiovascular effects of naloxone,naltrexone and morphine in the squirrel monkey

Heart rate (HR) and mean arterial blood pressure (BP) were recorded from conscious, chair-restrained squirrel monkeys surgically prepared with chronically indwelling arterial and venous catheters to determine the effects of acute intravenous injections of two opiate antagonists and an agonist. Naloxone (0.3–10.0 mg/kg) or naltrexone (0.3–10.0 mg/kg) had little effect on HR or BP during a 30-minute post-injection period. Morphine (3.0–5.6 mg/kg) produced biphasic effects comprising an initial decrease followed by an increase in HR, and an increase followed by a decrease in BP. Lower morphine doses had lesser effects during a 100-minute post-injection period. Pre-treatment with 0.03 mg/kg naloxone attenuated the depressive effect of morphine on HR and BP, but increases in HR and BP due to morphine were enhanced. Pretreatment with 0.3 mg/kg naloxone prevented morphine-induced decreases in HR and BP, yet increases in HR and BP persisted. In previous behavioral studies, morphine in combination with naloxone similarly increased rates of responding in the squirrel monkey. Together, these data suggest an effect of naloxone that goes beyond mere pharmacological antagonism of the effects of morphine.     

Hemodynamic response to anesthesia in pregnant and nonpregnant ICR mice

Mean arterial blood pressure (BP) and heart rate (HR) during and after recovery from anesthesia in pregnant and nonpregnant ICR mice were evaluated. Mice were evaluated during mechanical ventilation, from 15 to 60 min after induction of anesthesia. The anesthetic protocols were pentobarbital (80 mg/kg, given intraperitoneally [i.p.]); two low doses of ketamine and xylazine (90 mg/kg, 7.5 mg/kg, respectively, i.p., with a second dose given 20 min after the initial dose); and a single high dose of ketamine and xylazine (150 mg/kg, 12.5 mg/kg, respectively, i.p.). The BP was measured in the right carotid artery, using a fluid-filled catheter connected to a chamber containing a solid-state pressure transducer. Mechanical ventilation was performed via tracheotomy, using a normalized minute ventilation of 3.5 ml*min-1*g-1 for nonpregnant mice and 3.0 ml*min-1*g-1 for pregnant mice. Mean BP was lower and HR was higher in pregnant than in nonpregnant mice for each anesthetic protocol. Pentobarbital induced significantly greater tachycardia and hypotension than did the other protocols. The average BP and HR were similar between two low doses and a single high dose of ketamine and xylazine. During spontaneous breathing from 30 to 180 min after recovery from anesthesia by use of a single low dose, ketamine and xylazine induced similar HR profiles, but mean BP in pregnant mice recovered earlier than did that in nonpregnant mice. These results suggest that ketamine and xylazine induced adequate anesthesia for superficial surgical procedures in pregnant and nonpregnant mice while inducing small changes in HR and BP, and pregnancy resulted in a different hemodynamic reaction in response to ketamine and xylazine. These data will be useful for the design and interpretation of physiologic protocols using pregnant and nonpregnant genetically targeted mice.     

Regional differences of cardiovascular effects of diltiazem in the rat

The dose-response relations of the central and peripheral effects of diltiazem were studied in 26 anaesthetized rats. Measured were the heart rate (HR), atrioventricular conduction time (PR), mean arterial blood pressure (BP), carotid and renal blood flow (Fc, Fr) and the corresponding relative regional resistance (RRc, RRr). The effects were evaluated by their maxima regularly reached 15-20 s after the i.v. bolus administration. The minimum dose which produced a significant HR decrease and PR prolongation were 0.4 and 2.0 mg/kg, respectively. In the mg/kg dose range a transient second degree AV block was regularly recorded. The lethal dose (cardiac arrest) was 20 mg/kg. BP significantly already decreased after 4 micrograms/kg. The dose-dependent decrease of Fr matched the hypotensive effect in the whole range due to unchanged RRr. In contrast Fc invariably increased at lower doses reflecting the RRc decay. Only in the mg/kg dose range Fc decreased in accord with BP since RRc dropped to a constant value (50% of control) with each administration. The peripheral reactions were significantly augmented in rats with renovascular hypertension. It is concluded that, in this model, the peripheral effects of diltiazem evidently surpass the central ones. The regional difference between the inert renal and responsive carotid vasculature might be due to a different mode of regulation of the respective vascular tone, hypothetically reflecting different density of membrane, potential-dependent Ca2+ channels.     

Effects of CL 115,347, (+/-)-15-deoxy-16-hydroxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation

The effect of CL 115,347, a topically active antihypertensive PGE2 analog, and PGE2 on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001-0.2 mg/kg) dose-dependently decreased BP, while intravenously infused PGE2 (30 micrograms/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE2 (30 micrograms/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE2 modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, viz. CL 115,347 acts primarily on blood vessels while PGE2 acts on blood vessels and heart.     

Effects of CL 115,347, (±)-15-deoxy-16-vinyl-PGE2 methyl ester, on cardiovascular responses and plasma catecholamines in pithed stroke-prone spontaneously hypertensive rats during sympathetic stimulation

The effect of CL 115,347, a topically active antihypertensive PGE₂ analog, and PGE₂ on changes in blood pressure (BP), heart rate (HR) response and plasma epinephrine (E) and norepinephrine (NE) levels induced by stimulation of the sympathetic spinal cord outflow were studied in pithed stroke-prone spontaneously hypertensive rats (SHRSP). Surgical pithing significantly reduced plasma E but not NE levels suggesting that the sympathoadrenal medullary system differentially affects E and NE release. Sympathetic stimulation of the spinal cord of pithed SHRSP increased HR, BP, plasma E and NE levels. Topically applied CL 115,347 (0.001–0.1 mg/kg) dose-dependently decreased BP, while intravenously infused PGE₂ (30 μg/kg/min) did not alter BP except for a brief initial drop. Topical application of CL 115,347 (0.1 mg/kg) also inhibited BP responses to sympathetic stimulation without effects on HR or plasma E or NE levels. Intravenous infusion of PGE₂ (30 μg/kg/min) inhibited both BP and HR responses to spinal cord stimulation but did not alter plasma catecholamine levels. These studies in SHRSP suggest that CL 115,347 and PGE₂ modulate cardiovascular responses mainly via postjunctional effects, but act differently on the cardiovascular elements, CL 115,347 acts primarily on blood vessels while PGE₂ acts on blood vessels and heart.     

Effects of chronic treatment with 7-nitroindazole in hyperthyroid rats

This study analyzed the contribution of neuronal nitric oxide synthase (nNOS) to the hemodynamic manifestations of hyperthyroidism. The effects on hyperthyroid rats of the chronic administration of 7-nitroindazole (7-NI), an inhibitor of nNOS, were studied. Six groups of male Wistar rats were used: control, 7-NI (30 mg.kg-1.day-1 by gavage), T(4)50, T(4)75 (50 or 75 microg thyroxine.rat-1.day-1, respectively), T(4)50+7-NI, and T(4)75+7-NI. All treatments were maintained for 4 wk. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, pulse pressure (PP), and HR were measured in conscious rats, and morphological, metabolic, plasma, and renal variables were determined. Expression of nNOS in the hypothalamus of T(4)75 and control rats was analyzed by Western blot analysis. The response of mean arterial pressure (MAP) to pentolinium (10 mg/kg iv) was used to evaluate the sympathetic contribution to BP in T(4)75 and T(4)75+7-NI rats. T(4) produced an increased hypothalamic nNOS expression and dose-related increases in blood pressure (BP), HR, and PP vs. control rats. 7-NI did not modify BP or any other hemodynamic variable in normal rats. However, 7-NI produced a marked reduction in BP, HR, PP, and food and water intake in both hyperthyroid groups and improved creatinine clearance in the T(4)75 group. Pentolinium produced a greater MAP decrease in the T(4)75+7-NI than in the T(4)75 group. In conclusion, administration of 7-NI attenuates the hemodynamic and metabolic manifestations of hyperthyroidism, suggesting that nNOS contributes to the hyperdynamic circulation of this endocrine disease by modulating sympathetic activity.     

Chronic ethanol attenuates centrally-mediated hypotension elicited via α2-adrenergic,but not I1-imidazoline,receptor activation in female rats

AimsThis study dealt with the effect of chronic ethanol administration on hemodynamic responses elicited by α₂-adrenergic (α-methyldopa) or I₁-imidazoline (rilmenidine) receptor activation in telemetered female rats.Main methodsThe effects of α-methyldopa or rilmenidine on blood pressure (BP), heart rate (HR) and their variability were investigated in rats that received liquid diet without or with ethanol (5% w/v) for 12 weeks. To evaluate the effect of each drug on cardiovascular autonomic control (BP and HR variability) in the absence or presence of ethanol, three time-domain indices of hemodynamic variability were measured: (i) standard deviation of mean arterial pressure (SDMAP), (ii) standard deviation of beat-to-beat intervals, and (iii) root mean square of successive differences in R–R intervals.Key findingsIn liquid diet-fed control rats, i.p. rilmenidine (600 µg/kg) or α-methyldopa (100 mg/kg) reduced BP along with decreases and increases, respectively, in HR. Both drugs had no effect on HR variability but reduced BP variability (SDMAP), suggesting a reduced vasomotor sympathetic tone. Ethanol feeding attenuated reductions in BP and SDMAP evoked by α-methyldopa but not by rilmenidine.SignificanceWe conclude that chronic ethanol preferentially compromises α₂- but not I₁-receptor-mediated hypotension in female rats probably via modulation of vasomotor sympathetic activity. These findings highlight the adequacy of rilmenidine use to lower BP in hypertensive alcoholic females.     

Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats

Recently, a new member of the calcitonin gene-related peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified. AM2/IMD has been shown to have a vasodilator effect in mice and rats and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA), and renal blood flow (RBF) in conscious unrestrained rats relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin NH2-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA, and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The duration of BP, HR, and RSNA responses was longer with rAM (5 nmol/kg) than with rAM2 infusion, whereas the increases in RBF induced by rAM2 and rAM were similar in their amplitude and duration. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA but had no effect on RBF. Baroreceptor denervation suppressed, but did not diminish, the increases in HR and RSNA to rAM2. These findings indicate that the physiological roles of rAM2 and rAM are similar and that rAM2 also has a long-lasting vasodilator action on the renal vascular bed.     

Hemodynamic actions of endothelin in conscious and anesthetized dogs

The newly described endogenous peptide, endothelin, was administered to five chronically instrumented conditioned dogs. Endothelin produced significant and simultaneous increases in both heart rate (HR) and mean arterial pressure (MAP) in conscious dogs. Endothelin also produced significant increases in MAP in anesthetized animals. Ganglionic suppression induced by hexamethonium (10 mg/kg) and atropine (0.1 mg/kg) blocked HR responses and markedly inhibited the pressor responses to endothelin in conscious animals. These results suggest that endothelin in part acts to elevate blood pressure and heart rate through modification of autonomic nervous system tone. When endothelin and angiotensin II were administered in mole equivalent doses, angiotensin II produced a pressor response of greater magnitude than did endothelin in conscious animals.     

2-Deoxyglucose as a tool for analyzing the humoral component of the cardiovascular reaction to stress

Blood pressure (BP), heart rate (HR), adrenaline (A) and noradrenaline (NA) effects of 2-desoxyglucose (500 mg/kg i.v.) were studied in conscious chronically instrumented wistar rats. A and NA contents in the blood were estimated by HPLC with electrochemical detection. In 15-40 minutes after 2-DG administration it was 13-16-fold increase in A content, 1.7-1.9-fold increase in NA content. At the same time BP fell by 5 mm Hg and HR fell by 100 beats/min. Atropine blocked bradycardia but had no effect on BP. It is concluded that high levels of endogenous A during stress are not responsible for cardiovascular responses usually observed.     

Ghrelin modulates baroreflex-regulation of sympathetic vasomotor tone in healthy humans

Ghrelin, a neuropeptide originally known for its growth hormone-releasing and orexigenic properties, exerts important pleiotropic effects on the cardiovascular system. Growing evidence suggests that these effects are mediated by the sympathetic nervous system. The present study aimed at elucidating the acute effect of ghrelin on sympathetic outflow to the muscle vascular bed (muscle sympathetic nerve activity, MSNA) and on baroreflex-mediated arterial blood pressure (BP) regulation in healthy humans. In a randomized double-blind cross-over design, 12 lean young men were treated with a single dose of either ghrelin 2 μg/kg iv or placebo (isotonic saline). MSNA, heart rate (HR), and BP were recorded continuously from 30 min before until 90 min after substance administration. Sensitivity of arterial baroreflex was repeatedly tested by injection of vasoactive substances based on the modified Oxford protocol. Early, i.e., during the initial 30 min after ghrelin injection, BP significantly decreased together with a transient increase of MSNA and HR. In the course of the experiment (>30 min), BP approached placebo level, while MSNA and HR were significantly lower compared with placebo. The sensitivity of vascular arterial baroreflex significantly increased at 30-60 min after intravenous ghrelin compared with placebo, while HR response to vasoactive drugs was unaltered. Our findings suggest two distinct phases of ghrelin action: In the immediate phase, BP is decreased presumably due to its vasodilating effects, which trigger baroreflex-mediated counter-regulation with increases of HR and MSNA. In the delayed phase, central nervous sympathetic activity is suppressed, accompanied by an increase of baroreflex sensitivity.     

Presynaptic alpha-adrenoceptor regulation of transmitter release in the conscious rat

1. Blood pressure (BP) and heart rate (HR) were recorded in conscious, adrenal demedulated rats. The rats were subjected to a 1-min period of mild "stress", induced by jet-air directed into the experimental cage. The plasma content of noradrenaline (NA), dopamine (DA) and 3, 4-dihydroxy-phenylacetic acid (DOPAC) was determined 1 min after termination of "stress". 2. The presynaptic alpha 2-adrenoceptor antagonist yohimbine (YOH) (10(-7) - 10(-6) mol/kg, given 5 min prior to "stress") did not alter the increase in BP and HR, induced by "stress", when compared to control rats (receiving NaCl instead of YOH at the corresponding time). 3. Pre-treatment with atropine (ATR) (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl increased HR but not BP significantly in both groups of rats. "Stress", as above, gave a significant prolongation of the increase in HR in rats receiving YOH, when compared to control rats. The increase in BP was not significantly altered, compared to controls. 4. The neuronal re-uptake inhibitor desmethylimipramine (DMI) (0.1 mg/kg) was given together with ATR (2.5 mg/kg) 5 min before YOH (10(-6) mol/kg) or NaCl in one group of rats. This treatment induced a significant increase in HR but did not affect BP. "Stress", induced as above, extended the duration of the increase in HR in the YOH-treated rats, compared to controls. The increase in BP was not significantly different between the YOH-treated rats and the controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorespiratory responses to interleukin-1beta in adult rats: role of nitric oxide, eicosanoids and glucocorticoids

Interleukin-1beta (IL-1beta) receptors are abundantly expressed in brain stem regions involved in respiratory control. We hypothesized that systemic administration of IL-1beta would increase ventilation (V(E )), and that nitric oxide, eicosanoids, and glucocorticoid receptors would modulate IL-1beta-induced cardioventilatory responses. Intravenous injections of three doses (37.5 ng kg(-1), 75 ng kg(-1 ) and 150 ng kg(-1)) of IL-1b induced monophasic increases in (V(E)), heart rate (HR), and blood pressure (BP) which had a distinctly different onset and duration of action compared to IL-1beta-induced body temperature elevations. Pre-treatment with the nitric oxide inhibitor L-NAME was associated with decreased peak V(E) responses, without affecting the latency and duration of IL-1beta. L-NAME also enhanced HR responses while pressor responses were attenuated. Eicosanoid inhibition with indomethacin resulted in markedly attenuated V responses. However, cardiovascular responses to IL-1beta were not modified by indomethacin. In contrast, pre-treatment with dexamethasone, was not associated with any changes in the IL-1beta-induced V(E), HR, or BP responses. We conclude that IL-1beta increases of V(E) are dose-dependent and are not time-locked with the pyrexic response suggesting the possibility that distinct neural pathways may underlie these responses. In addition, nitric oxide and eicosanoid-dependent mechanisms modulate IL-1beta ventilatory effects.     

Haemodynamic Responses to Selective Vagal Nerve Stimulation under Enalapril Medication in Rats

Selective vagal nerve stimulation (sVNS) has been demonstrated to lower blood pressure (BP) in rats without causing major side effects. This method might be adapted for the treatment of therapy-resistant hypertension in patients. Converting enzyme inhibitors (CEIs) are among the first drugs that are administered for arterial hypertension and prominently reduce BP primarily by interacting with the renin-angiotensin system of the kidneys. Beyond the reduction of BP, CEI have a positive effect on the survival rate after myocardial infarction; they reduce the rates of stroke and improve the neurohormonal status in heart-failure patients. If sVNS might be introduced as a therapy against resistant hypertension, patients will at least partially stay on their CEI medication. It is therefore the aim of this study to investigate the influence of the CEI enalapril on the haemodynamic and respiratory effects of sVNS. In 10 male Wistar rats, a polyimide-based multichannel-cuff-electrode was placed around the vagal nerve bundle to selectively stimulate the aortic depressor nerve fibres. Stimulation parameters were adapted to the thresholds of the individual animals and included repetition frequencies between 30 and 50 Hz, amplitudes of 0.5 to 1.5 mA and pulse widths between 0.4 ms and 1.0 ms. BP responses were detected with a microtip transducer in the left carotid artery, and electrocardiography was recorded with subcutaneous electrodes. After intravenous administration of enalapril (2 mg/kg bodyweight), the animals’ mean arterial blood pressures (MAPs) decreased significantly, while the heart rates (HRs) were not significantly influenced. The effects of sVNS on BP and HR were attenuated by enalapril but were still present. We conclude that sVNS can lower the MAP during enalapril treatment without relevant side effects.     

Nitric oxide modulates arterial baroreflex control of heart rate in conscious lambs in an age-dependent manner

Experiments were carried out in conscious chronically instrumented lambs aged 1 (n = 6) and 6 wk (n = 5) to evaluate the arterial baroreflex control of heart rate (HR) during postnatal maturation and to investigate any modulatory role of endogenously produced nitric oxide (NO). Before and after intravenous administration of 20 mg/kg of the L-arginine analog N(G)-nitro-L-arginine methyl ester (L-NAME), the arterial baroreflex was assessed by measuring HR responses to increases and decreases in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. The HR range over which the baroreflex operates and minimum HR as well as maximum gain were greater at 1 than at 6 wk of age. These age differences were abolished in the presence of L-NAME, which decreased the HR range and gain of the arterial baroreflex control of HR at 1 but not at 6 wk of age. These data provide new information that age-dependent effects of the arterial baroreflex appear to result from effects of endogenously produced NO.     

The cardiovascular effects of PFRFamide and PFR(Tic)amide, a possible agonist and antagonist of neuropeptide FF (NPFF)

Neuropeptide FF (NPFF), an endogenous opioid-related neuromodulater, has been reported to show significant effects on the cardiovascular system, namely elevation of arterial blood pressure (BP) and heart rate (HR) in rats. In the present study, we synthesized two novel NPFF analogs, PFRFamide (putative NPFF agonist) and PFR(Tic)amide (putative NPFF antagonist), and examined their cardiovascular effect on BP and HR in anesthetized rats. The arterial mean BP and HR were measured by way of direct femoral artery catheterization. The data showed that PFRFamide increased BP in a dose-dependent manner, while PFR(Tic)amide decreased BP dose-dependently. These results revealed the possibility of PFRFamide and PFR(Tic)amide to be NPFF agonist and antagonist (or inverse agonist), respectively. These two NPFF analogs may possess potential in new drug design, and the NPFF system could be very important in mammalian cardiovascular function.     

Changes in the autonomic balance of the regulation of the rate of heart contractions during physical loading in chronic suppression or potentiation of the endogenous opioidergic system in rats

The influence of endogenous opioid system on the rat's mean blood pressure (BP) and heart rate (HS) has been studied under the chronic infusion of the opioid receptor antagonist naloxone (1 mg/kg intraperitoneally, twice a day, during 6 days) or an inhibitor of captorile enkephalinases (20 mg/kg subcutaneously). Naloxone caused a significant decrease and captorile--increase of maximum meanings of HR during exercises (the running on the treadmill during 3.5 min by the velocity of 30 m/min), both compounds didn't exert a considerable effect on BP at rest and during exercises. It has been concluded that the endogenous opioid system plays an important role in the autonomic HR regulation during exercise.     

A comparison of ketamine/xylazine and ketamine/xylazine/acepromazine anesthesia in the rabbit

Parenteral anesthetic combinations such as ketamine and xylazine have become the agents of choice for anesthesia in the rabbit, because they are effective, easily administered and inexpensive. A number of recent reports have recommended including acepromazine in this combination, but a critical evaluation of this combination in the rabbit has not been reported. Five adult New Zealand white rabbits were anesthetized intramuscularly with ketamine (35 mg/kg) and xylazine (5 mg/kg) with or without acepromazine (0.75 mg/kg). The study was conducted in a double blind fashion, where each rabbit was administered both combinations at a minimum of 7 day intervals. Physiologic parameters were evaluated including heart rate, respiratory rate, central arterial blood pressure, pedal, palpebral and postural reflex activity. The duration of general anesthesia, estimated by the time elapsed between the loss and return of the palpebral reflex, was greater (means = 99 +/- 20 minutes) when acepromazine was employed in the combination compared to (means = 77 +/- 5 minutes) when ketamine/xylazine were used alone. Mean central arterial blood pressure reached a lower level when acepromazine was utilized (means = 46 +/- 8 mm/Hg) than when it was not (means = 57 +/- 12 mm/Hg.). The addition of acepromazine in a ketamine/xylazine combination resulted in a 28% longer period of anesthesia, a 19% lower mean central arterial blood pressure and a 32% longer recovery of postural reflexes. The ketamine/xylazine/acepromazine combination is a useful regimen for normovolemic animals when anesthetic duration greater than that produced by ketamine/xylazine alone is required.     

Gender Dependency of Circadian Blood Pressure and Heart Rate Profiles in Spontaneously Hypertensive Rats: Effects of Beta‐Blockers

This study investigated (i) blood pressure (BP), heart rate (HR), and their relation to urinary NOx and eNOS protein expression in male and female spontaneously hypertensive rats (SHR), as well as (ii) gender‐dependent cardiovascular effects of nebivolol (NEB) in comparison to metoprolol (MET) in SHR. BP and HR were measured telemetrically after a single intraperitoneal application of NEB or MET at 07.00 and 19.00 h in male rats and at 19.00 h in proestrus female rats. The two β‐blockers varied in time of decreasing BP and HR and also in duration. In males, MET decreased BP and HR for few hours exclusively when applied at the onset of the activity phase (i.e., at 19.00 h), while after its application at 07.00 h, BP and HR were unchanged. In females, MET also caused a short‐lasting BP and HR reduction, with the effect being more pronounced than in males. In males, NEB at either dosing time decreased HR and BP to a greater extent than did MET. This effect was evident both during the activity and rest periods and persisted for at least five days. In females, NEB provoked a similar, but more pronounced, effect on BP and HR in comparison to males. These findings demonstrate that significant gender‐dependent differences in the circadian profile of BP and HR exist. BP and urinary NOx as well as eNOS expression are inversely correlated, and the cardiovascular effects of NEB and MET vary, depending on the time of application as well as gender.