Blood pressure and other physiological responses in awake and anesthetized guinea pigs

The effect of combinations of injectable anesthetics on mean arterial blood pressure, blood gases, heart rate and respiration of the guinea pig (NIH Outbred strain) was investigated. After a 30 minute period in which baseline resting cardiorespiratory measurements were obtained, five groups of six pigmented animals having indwelling carotid cannulas were anesthetized with (a) ketamine hydrochloride (30 mg/kg, im)/xylazine (5 mg/kg, im); (b) sodium pentobarbital (15 mg/kg, ip)/fentanyl-droperidol (0.4 mg/kg, im); (c) diazepam (5mg/kg, ip)/fentanyl citrate (0.32 mg/kg, im); (d) diazepam (5 mg/kg, ip)/alphaxalone-alphadolone acetate (45 mg/kg, im); or (e) 1% alpha-chloralose-40% urethane (0.8 ml/100g, ip). Animals were not respirated artificially and no supplemental doses of anesthetic were given. Resting blood pressure in awake animals was measured over time for as long as cannulas remained patent (109 measurements). Mean resting blood pressure, for this strain of guinea pigs, was determined to be 53.1 +/- 4.2 mmHg. There was no indication that mean arterial blood pressure changed with age in animals varying in weight from 215 g to 550 g. Under diazepam/fentanyl, blood pressure rose significantly above resting level to a mean of 71.1 +/- 6.1 mmHg. With the other four combinations, blood pressure stabilized near, but below pre-anesthesia levels (ketamine/xylazine 47.1 +/- 6.8 mmHg; pentobarbital/fentanyl-droperidol, 46.9 +/- 3.2 mmHg; diazepam/alphaxalone-alphadolone, 47.8 +/- 4.8 mmHg; chloralose-urethane, 51.0 +/- 1.2 mmHg). Under diazepam/alphaxalone-alphadolone and chloralose-urethane, respiration was depressed and blood gas levels deviated from normal to the extent that artificial ventilation would be necessary to maintain an adequate physiological state.     

Sleep-dependent changes in the coupling between heart period and blood pressure in human subjects

We investigated whether in human subjects, the pattern of coupling between the spontaneous fluctuations of heart period (HP) and those of systolic blood pressure (SBP) differs among wake-sleep states. Polysomnographic recordings and finger blood pressure measurements were performed for 48 h in 15 nonobese adults without sleep-disordered breathing. The cross-correlation function (CCF) between the fluctuations of HP and SBP at frequencies <0.15 Hz was computed during quiet wakefulness (QW), light (stages 1 and 2) and deep (stages 3 and 4) nonrapid-eye-movement sleep (NREMS), and rapid-eye-movement sleep (REMS). A positive correlation between HP and the previous SBP values, which is the expected result of baroreflex feedback control, was observed in the sleep states but not in QW. In deep NREMS, the maximum CCF value was significantly higher than in any other state, suggesting the greatest baroreflex contribution to the coupling between HP and SBP. A negative correlation between HP and the subsequent SBP values was also observed in each state, consistent with the mechanical feed-forward action of HP on SBP and with central autonomic commands. The contribution of these mechanisms to the coupling between HP and SBP, estimated from the minimum CCF value, was significantly lower in deep NREMS than either in light NREMS or QW. These results indicate that the pattern of coupling between HP and SBP at low frequencies differs among wake-sleep states in human subjects, with deep NREMS entailing the highest feedback contribution of the baroreflex and a low effectiveness of feed-forward mechanisms.     

Relationship between body fluid volumes and arterial pressure

The mechanisms by which blood volume influences arterial pressure in situations of reduced excretory capacity are reviewed. The relationships between volume and arterial pressure are discussed as acute, transitional, and long-term phases, recognizing that they are part of a continuum of events leading to a steady state. The acute hydraulic effects, reflex and hormonal responses, and local autoregulatory responses and their interactions are reviewed. Important functional changes of the microcirculation that occur in the transitional phase (1-2 days) are presented. These include increased O2 sensitivity, elevated tone, increased vasomotion, and functional rarefaction, all of which appear to be mediated at the local tissue level. In situation of long-term chronic volume expansion, some of these functional changes evolve into permanent structural changes such as anatomical rarefaction. However, increased vascular sensitivity to oxygen remains. These changes appear to account for a maintained increase in total peripheral resistance with hypertension, which is sustained at relatively normal levels of blood volume and cardiac output.     

Circulating endothelin parallels arterial blood pressure during sleep in healthy subjects

OBJECTIVE: To characterize plasma endothelin 1 (ET-1) and arterial blood pressure (ABP) time courses during the first complete non-rapid eye movement (NREM)-REM sleep cycle in healthy subjects, together with plasma renin activity (PRA) and plasma atrial natriuretic peptide (ANP). METHODS: Heart rate (HR), intra-arterial blood pressure and sleep electroencephalographic activity were recorded continuously during the night in eight healthy 20-28-year-old males. Blood was sampled every 10 min during their first complete sleep cycle for simultaneous measurements of plasma ET-1, PRA and ANP. RESULTS: Circulating ET-1 demonstrated significant variations during the sleep cycle (p<0.0001) that paralleled those of ABP (p<0.05) and HR (p<0.005), with a minimum during NREM sleep and a maximum during REM sleep. ET-1 time course opposed that of PRA which increases during NREM sleep and decreases during REM sleep (p<0.0005). Plasma ANP did not demonstrate systematic variation in relation with the sleep cycle. CONCLUSION: Circulating ET-1, which parallels variations of ABP, may participate in ABP regulation during sleep in healthy subjects, in association with the renin-angiotensin system.     

Pressure diuresis mechanism in the control of renal function and arterial pressure

Precise knowledge of the interrelationships between arterial pressure and urinary excretion of sodium and water is crucial to understanding the long-term control of arterial pressure. Although increases in renal perfusion pressure have been known for more than 35 years to inhibit tubular reabsorption, the mechanism of this pressure diuresis response, the humoral or physical factors involved, and even the nephron segments in which the changes in tubular function occur remain relatively unknown. This review focuses on the experimental evidence that supports current hypotheses concerning the mechanism of pressure diuresis. Specifically, it examines the possibility that pressure diuresis is caused by a small increase in glomerular filtration rate, alterations in the humoral or physical factors regulating proximal tubular reabsorption, and/or inhibition of tubular reabsorption in deep nephrons secondary to changes in hemodynamics in juxtamedullary nephrons. The concept originally proposed that the kidney serves as the dominant long-term controller of arterial pressure is largely based on the assumptions that the pressure diuresis phenomenon exists and that it occurs via a nonadaptive mechanism. It has been proposed that hypertension can develop only if the relationship between arterial pressure and sodium excretion is shifted toward higher pressures. The remainder of this review examines recent evidence indicating that an abnormality in the pressure natriuresis relationship may be associated with the development of hypertension in humans and in the genetic rat models of the disease.     

The effects of ethanol on pancreatic blood flow in awake and anesthetized dogs

The pathophysiology of alcohol-induced acute pancreatitis is not clear. Ischemic injury has been suggested as a possible mechanism. To examine the effects of ethanol on pancreatic and splanchnic blood flow, measurements were made in fasted, conditioned awake dogs before and after iv infusion of ethanol (1.7 g/kg). At 30 min blood ethanol concentration ranged between 60 and 150 mg/dl and at 60 min between 166 and 350 mg/dl. Although cardiac output, aortic pressure, left atrial pressure, and arterial pH did not change, pancreatic flow declined by 39 +/- 12 ml/min/100 g, P less than 0.05 (from 173 +/- 10 ml/min/100 g) at 30 min and was still depressed (by 27 +/- 12 ml/min/100 g, P less than 0.05) at 60 min. Concomitantly, hepatic arterial flow increased. While hepatic and pancreatic flow changed inversely, the correlation (r = -0.17) of these changes was not significant. At comparable blood ethanol concentrations in pentobarbital-anesthetized dogs hepatic arterial flow increased by 11 +/- 3 ml/min/100 g, P less than 0.01 (from 24 +/- 5 ml/min/100 g), but pancreatic flow did not change. Thus, in the awake dog at blood levels that would produce mild to moderate alcoholic intoxication in man, ethanol reduces pancreatic flow. Although hepatic flow increases concomitantly, the relationship of these changes appears to be independent.     

Dynamic interactions between arterial pressure and sympathetic nerve activity: role of arterial baroreceptors

The role of arterial baroreceptors in controlling arterial pressure (AP) variability through changes in sympathetic nerve activity was examined in conscious rats. AP and renal sympathetic nerve activity (RSNA) were measured continuously during 1-h periods in freely behaving rats that had been subjected to sinoaortic baroreceptor denervation (SAD) or a sham operation 2 wk before study (n = 10 in each group). Fast Fourier transform analysis revealed that chronic SAD did not alter high-frequency (0.75-5 Hz) respiratory-related oscillations of mean AP (MAP) and RSNA, decreased by approximately 50% spectral power of both variables in the midfrequency band (MF, 0.27-0.74 Hz) containing the so-called Mayer waves, and induced an eightfold increase in MAP power without altering RSNA power in the low-frequency band (0.005-0.27 Hz). In both groups of rats, coherence between RSNA and MAP was maximal in the MF band and was usually weak at lower frequencies. In SAD rats, the transfer function from RSNA to MAP showed the characteristics of a second-order low-pass filter containing a fixed time delay ( approximately 0.5 s). These results indicate that arterial baroreceptors are not involved in production of respiratory-related oscillations of RSNA but play a major role in the genesis of synchronous oscillations of MAP and RSNA at the frequency of Mayer waves. The weak coupling between slow fluctuations of RSNA and MAP in sham-operated and SAD rats points to the interference of noise sources unrelated to RSNA affecting MAP and of noise sources unrelated to MAP affecting RSNA.     

Introduction of a new regulatory mechanism into human hemoglobin

Previous studies on bovine hemoglobin (HbBv) have suggested amino acid substitutions, which might introduce into human hemoglobin (HbA) functional characteristics of HbBv, namely a low intrinsic oxygen affinity regulated by Cl(-). Accordingly, we have constructed and characterized a multiple mutant, PB5, [beta(V1M + H2 Delta + T4I + P5A + A76K)] replacing four amino acid residues of HbA with those present at structurally analogous positions in HbBv, plus an additional substitution, beta T4I, which does not occur in either HbBv or HbA. This 'pseudobovine' hemoglobin has oxygen binding properties very similar to those of HbBv: the P(50) of HbA, PB5 and HbBv in the absence of Cl(-) are 1.6, 4.6 and 4.8 torr, respectively, and in 100 mM Cl(-) are 3.7, 10.5 and 12 torr, respectively. Moreover, PB5 has 3-fold slower autoxidation rate compared to HbA and HbBv. These are desirable characteristics for a human hemoglobin to be considered for use as a clinical artificial oxygen carrier. Although the functional properties of PB5 and HbBv are similar, van't Hoff plots indicate that the two hemoglobins interact differently with water, suggesting that factors regulating the R to T equilibrium are not the same in the two proteins. A further indication that PB5 is not a functional mimic of HbBv derives from PB5(control), a human hemoglobin with the same substitutions as PB5, except the beta T4I replacement. PB5(control) has a high oxygen affinity (P(50)=2.3 torr) in the absence of Cl(-), but retains the Cl(-) effect of PB5. The Cl(-) regulation of oxygen affinity in PB5 involves lysine residues at beta 8 and beta 76. PB4, which has the same substitutions as PB5 except beta A76K, and PB6, which has all the substitutions of PB5 plus beta K8Q, both have a low intrinsic oxygen affinity, like HbBv and PB5, but exhibit a decreased sensitivity to Cl(-). Since HbBv has lysine residues at both beta 8 and beta 76, these results imply that Cl(-) regulation in HbBv likewise involves these two residues. The mechanism responsible for the low intrinsic oxygen affinity of HbBv remains unclear. It is suggested that residues peculiar to HbBv at the alpha(1)beta(1) interface may play a role.     

Comparative study of interneuronal relations in the auditory cortex of awake and anesthetized cats

The character of interneuronal relations in the auditory cortex of alert and anaesthetized cats (nembutal) with chronicly inplanted electrodes was studied with the method of statistic analysis of cross-intervals of the two impulse series. The analysis of the histograms, obtained by means of processing a neuronal activity, showed that nembutal did not eliminate the dependent relations between neurones and that in the majority of cases the types of these relations are either retained or supplemented with new components. Experiments with a reduced dose of nembutal permitted to trace in time the changes in the amount of the inhibitory and excitatory interrelations in the anaesthetized state, and to compare these changes to the changes in the frequency of spike activity. It was found that nembutal predominantly suppresses the activity of the neurones, generating small spikes. The number of inhibitory connections is reduced simultaneously. Such synchroneity permits to assume the participation of the neurones generating small spikes in the establishment of inhibitory interrelations in the cat auditory cortex.     

Effect of dl-propranolol and l-and d-alprenolol on arterial pressure in awake or anesthesized, normo- or hypertensive rats]

Intravenous administration of dl-propranolol, l-and d-alprénolol in normotensive and spontaneous, renal or neurogen hypertensive rats induced decrease of blood pressure in anaesthetized animals. In awake animals hypotensive activity was irregular and lower.     

The effect of secretin on pancreatic blood flow in the awake and anesthetized dog

The canine pancreatic blood flow was studied after iv secretin (resulting in a plasma level commensurate with the postcibal state), and also after larger iv doses and after duodenal acidification. We found that blood flow was unaffected by "physiological" doses of secretin, or by perfusion of duodenum at a pH as low as 2.0, but increased by bolus doses (0.5 CU/kg and above), and by acidification to pH 1.4. Anesthesia does not affect the blood flow response although the bicarbonate response appeared to be blunted under anesthesia. We conclude that increase in pancreatic blood flow is not a physiological effect of secretin.