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Biomedical subjects

N C Gonzalez

Publications and source records attributed to N C Gonzalez.

At least 19 recordsLinked to original sources
PubMed2001

Leukocyte-endothelial interactions in environmental hypoxia.

Hypoxia induced by reducing inspired PO2 (PIO2) to 70 Torr, promotes a rapid microvascular response characterized by increased leukocyte rolling and adherence to the venular endothelium, leukocyte emigration to the perivascular space and increased vascular permeability. This appears to be a generalized response since it is observed in venules of the mesentery, cremaster muscle and pial microcirculations. After three weeks of acclimatization to hypoxia (barometric pressure 380 Torr, PIO2 70 Torr), the initial microvascular response resolves and exposure to even lower PIO2 (50 Torr) fails to elicit a microvascular response. The initial response is accompanied by a reversible increase in the generation of reactive oxygen species (ROS) and is blocked by antioxidants and by interventions that increase the tissue levels of nitric oxide (NO). In contrast to ischemia/reperfusion, ROS levels increase during hypoxia and return towards pre-hypoxic values after return to normoxia. Acclimatization involves upregulation of inducible NO synthase (iNOS): inhibition of iNOS using two different antagonists results in increased leukocyte-endothelial interactions and increased ROS generation. The results suggest that hypoxia initially leads to an alteration of the ROS/NO balance which is eventually restored during the acclimatization process. This phenomenon may have relevance to the microcirculatory alterations associated with hypoxic exposure, including acute mountain sickness and high altitude pulmonary and cerebral edema.

Altitude Sickness↗
PubMed2001

Redistribution of pulmonary blood flow during hypoxic exercise.

Pulmonary blood flow (PBF) distribution was studied at rest and during exercise in rats acclimatized to chronic hypoxia (barometric pressure [PB] 370 Torr for 3 weeks, A rats) and non-acclimatized (NA) littermates. Both A and NA rats exercised in hypoxia (inspired O2 pressure [PIO2] approximately 70 Torr) or in normoxia (PlO2 approximately 145 Torr). PBF distribution was determined using fluorescent-labeled microspheres injected into the right atrium. The lungs were cut into 28 samples to determine relative scatter of specific PBF ([sample fluorescence intensity/sample dry weight)/(total lung fluorescence intensity/total lung dry weight]). Exercise produced redistribution of PBF both in NA and A rats, and this effect was larger in hypoxia than in normoxia, with minimal redistribution occurring during normoxic exercise in NA rats. The pattern of distribution varies considerably among individual animals. As a result of distribution, the previous high flow areas would be overperfused during hypoxic exercise in some rats. The results support the concept that hypoxic pulmonary vasoconstriction is not uniform and suggest that the combination of hypoxia and exercise may lead to overperfusion and capillary leak in some individuals.

Acclimatization↗
PubMed2001

Myocardial adrenergic and cholinergic receptor function in hypoxia: correlation with O(2) transport in exercise.

The time course of changes in rat myocardial alpha(1)- and beta-adrenoceptors and of muscarinic cholinergic (M-Ach) receptor characteristics was studied parallel with the changes in exercise systemic O(2) transport during a 21-day period of hypoxia (barometric pressure 380 Torr) to assess the effects of receptor modification during acclimatization on maximal exercise capacity. Hypoxia resulted in polycythemia, pulmonary hypertension, right ventricular hypertrophy, and transient left ventricular weight loss. Maximal O(2) consumption at 30 min of hypoxia was reduced to 60% of the normoxic value and remained unchanged. This was partly due to a gradual decrease in maximal cardiac output and heart rate (HR(max)), which offset the increase in blood O(2) content. HR(max) correlated positively (r = 0.994) with beta-adrenoceptor density and negatively (r = -0.964) with M-Ach-receptor density, suggesting that HR(max) reduction results from intrinsic changes in myocardial receptor characteristics leading to reduced responses to adrenergic stimulation and elevated responses to cholinergic stimulation. alpha-Adrenoceptor density in both ventricles increased initially to eventually fall below normoxic values. The dissociation between the different patterns of right and left ventricular weight and the similar pattern of alpha-adrenoceptor change in both ventricles do not support a role for these receptors on right ventricular myocardial hypertrophy.

Acclimatization↗
PubMed2001

Living and training in moderate hypoxia does not improve VO2 max more than living and training in normoxia.

The objective of these experiments was to determine whether living and training in moderate hypoxia (MHx) confers an advantage on maximal normoxic exercise capacity compared with living and training in normoxia. Rats were acclimatized to and trained in MHx [inspired PO2 (PI(O2)) = 110 Torr] for 10 wk (HTH). Rats living in normoxia trained under normoxic conditions (NTN) at the same absolute work rate: 30 m/min on a 10 degrees incline, 1 h/day, 5 days/wk. At the end of training, rats exercised maximally in normoxia. Training increased maximal O2 consumption (VO2 max) in NTN and HTH above normoxic (NS) and hypoxic (HS) sedentary controls. However, VO2 max and O2 transport variables were not significantly different between NTN and HTH: VO2 max 86.6 +/- 1.5 vs. 86.8 +/- 1.1 ml x min(-1) x kg(-1); maximal cardiac output 456 +/- 7 vs. 443 +/- 12 ml x min(-1) x kg(-1); tissue blood O2 delivery (cardiac output x arterial O2 content) 95 +/- 2 vs. 96 +/- 2 ml x min(-1) x kg(-1); and O2 extraction ratio (arteriovenous O2 content difference/arterial O2 content) 0.91 +/- 0.01 vs. 0.90 +/- 0.01. Mean pulmonary arterial pressure (Ppa, mmHg) was significantly higher in HS vs. NS (P < 0.05) at rest (24.5 +/- 0.8 vs. 18.1 +/- 0.8) and during maximal exercise (32.0 +/- 0.9 vs. 23.8 +/- 0.6). Training in MHx significantly attenuated the degree of pulmonary hypertension, with Ppa being significantly lower at rest (19.3 +/- 0.8) and during maximal exercise (29.2 +/- 0.5) in HTH vs. HS. These data indicate that, despite maintaining equal absolute training intensity levels, acclimatization to and training in MHx does not confer significant advantages over normoxic training. On the other hand, the pulmonary hypertension associated with acclimatization to hypoxia is reduced with hypoxic exercise training.

Altitude↗
PubMed2001

Leukotriene B(4) promotes reactive oxidant generation and leukocyte adherence during acute hypoxia.

Acute systemic hypoxia produces rapid leukocyte adherence in the rat mesenteric microcirculation, although the underlying mechanisms are not fully known. Hypoxia is known to increase reactive oxygen species (ROS) generation, which could result in formation of the lipid inflammatory mediator leukotriene B(4) (LTB(4)). The goal of this study was to examine the role of LTB(4) in hypoxia-induced microvascular alterations. Using intravital microscopy, we determined the effect of the LTB(4) antagonist, LTB(4)-dimethyl amide (LTB(4)-DMA), on ROS generation and leukocyte adherence in mesenteric venules during hypoxia. Exogenous LTB(4) increased ROS generation to 144 +/- 8% compared with control values and also promoted leukocyte adherence. These responses to LTB(4) were blocked by pretreating the mesentery with LTB(4)-DMA. Leukopenia did not significantly attenuate the LTB(4)-induced increase in ROS generation (142 +/- 12.1%). LTB(4)-DMA substantially, though not completely, reduced hypoxia-induced ROS generation from 66 +/- 18% to 11 +/- 4% above control values. Hypoxia-induced leukocyte adherence was significantly attenuated by LTB(4)-DMA. Our results support a role for LTB(4) in the mechanism of hypoxia-induced ROS generation and leukocyte adherence in the rat mesenteric microcirculation.

Acute Disease↗
PubMed2001

Exercise training alters the effect of chronic hypoxia on myocardial adrenergic and muscarinic receptor number.

Chronic hypoxic exposure results in elevated sympathetic activity leading to downregulation of myocardial alpha(1)- and beta-adrenoceptors (alpha(1)-AR, beta-AR). On the other hand, it has been shown that sympathetic activity is reduced by exercise training. The objective of this study was to determine whether exercise training could modify the changes in receptor expression associated with acclimatization. Four groups of rats were studied: normoxic sedentary rats (NS), rats living and training in normoxia (NTN), sedentary rats living in hypoxia (HS, inspired PO(2) = 110 Torr), and rats living and training in hypoxia (HTH, inspired PO(2) = 110 Torr). Training consisted of running in a treadmill at 80% of maximal O(2) uptake during 10 wk. Myocardial receptor density was measured by radioactive ligand binding. Right ventricular (RV) hypertrophy occurred in HS but not in HTH. No effect of exercise was detected in RV weight of normoxic rats. Acclimatization to hypoxia (HS vs. NS) resulted in a decrease in both alpha(1)- and beta-AR density, whereas muscarinic receptor (M-Ach) expression increased. Hypoxic exercise training (HS vs. HTH) moderated beta-AR downregulation and M-Ach upregulation and prevented the fall in alpha(1)-AR density. Normoxic training (NS vs. NTN) did not change beta-AR density. On the other hand, densities of alpha(1)-AR in both ventricles as well as RV M-Ach increased in NTN vs. NS. The data show that exercise training in hypoxia 1) prevents RV hypertrophy, 2) suppresses the downregulation of alpha(1)-AR in the left ventricle (LV) and RV, and 3) attenuates the changes in both beta-AR and M-Ach receptor density in LV and RV. Exercise training in normoxia increases M-Ach receptor expression in the RV.

Animals↗
PubMed2000

Acute vs. chronic effects of elevated hemoglobin O(2) affinity on O(2) transport in maximal exercise.

These studies were conducted to compare the effects on systemic O(2) transport of chronically vs. acutely increased Hb O(2) affinity. O(2) transport during maximal normoxic and hypoxic [inspired PO(2) (PI(O(2))) = 70 and 55 Torr, respectively] exercise was studied in rats with Hb O(2) affinity that was increased chronically by sodium cyanate (group 1) or acutely by transfusion with blood obtained from cyanate-treated rats (group 2). Group 3 consisted of normal rats. Hb O(2) half-saturation pressure (P(50); Torr) during maximal exercise was approximately 26 in groups 1 and 2 and approximately 46 in group 3. In normoxia, maximal blood O(2) convection (TO(2 max) = cardiac output x arterial blood O(2) content) was similar in all groups, whereas in hypoxia TO(2 max) was significantly higher in groups 1 and 2 than in group 3. Tissue O(2) extraction (arteriovenous O(2) content/arterial O(2) content) was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05) at all exercise PI(O(2)) values. In normoxia, maximal O(2) utilization (VO(2 max)) paralleled O(2) extraction ratio and was lowest in group 1, intermediate in group 2, and highest in group 3 (P < 0.05). In hypoxia, the lower O(2) extraction ratio values of groups 1 and 2 were offset by their higher TO(2 max); accordingly, their differences in VO(2 max) from group 3 were attenuated or reversed. Tissue O(2) transfer capacity (VO(2 max)/mixed venous PO(2)) was lowest in group 1 and comparable in groups 2 and 3. We conclude that lowering Hb P(50) has opposing effects on TO(2 max) and O(2) extraction ratio, with the relative magnitude of these changes, which varies with PI(O(2)), determining VO(2 max). Although the lower O(2) extraction ratio of groups 2 vs. 3 suggests a decrease in tissue PO(2) diffusion gradient secondary to the low P(50), the lower O(2) extraction ratio of groups 1 vs. 2 suggests additional negative effects of sodium cyanate and/or chronically low Hb P(50) on tissue O(2) transfer.

Animals↗
PubMed2000

Systemic hypoxia increases leukocyte emigration and vascular permeability in conscious rats.

We recently observed that acute systemic hypoxia produces rapid increases in leukocyte adherence in the mesenteric microcirculation of the anesthetized rat Wood JG, Johnson JS, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 1734-1740, 1999; Wood JG, Mattioli LF, and Gonzalez NC. J Appl Physiol 87: 873-881, 1999. Hypoxia-induced leukocyte adherence is associated with an increase in reactive oxygen species (ROS) generation and is attenuated by antioxidants or interventions that increase tissue levels of nitric oxide (NO). These results suggest that the acute effects of hypoxia on leukocyte-endothelial interactions are caused by a change in the ROS-NO balance. The present experiments were designed to extend our observations of the initial microcirculatory response to hypoxia; specifically, we wanted to determine whether the response to systemic hypoxia involves increased microvascular permeability and leukocyte emigration and whether ROS generation and decreased NO levels contribute to these responses. At this time, there is conflicting evidence, from in vitro studies, regarding the effect of hypoxia on these indexes of vascular function. Our studies were carried out in the physiological setting of the conscious animal, in which a prolonged hypoxic exposure is possible without the adverse effects that may develop under anesthesia. The central observation of these studies is that conscious animals exposed for 4 h to environmental hypoxia show increased microvascular permeability and emigration of leukocytes into the extravascular space of the mesenteric circulation. Furthermore, these events are dependent on increased ROS generation and, possibly, a subsequent decrease in tissue NO levels during systemic hypoxia. Our results show that systemic hypoxia profoundly affects vascular endothelial function through changes in the ROS-NO balance in the conscious animal.

Animals↗
PubMed1999

Splenic contraction-induced reversible increase in hemoglobin concentration in intermittent hypoxia.

The effect of intermittent hypoxia (IHx) on blood hemoglobin concentration ([Hb]) and the underlying mechanisms were studied in rats exposed to 10% O2, 1 h/day, for up to 5 wk. IHx protocols with longer daily hypoxic exposure show persistent polycythemia; however, it is unknown whether [Hb] increases transiently during hypoxia in protocols without polycythemia. Hypoxia produced a reversible [Hb] increase after 4 days of IHx but not in normoxic controls (NxC) or after shorter period of IHx. Splenectomy abolished the phenomenon. Plasma epinephrine and norepinephrine levels during hypoxia were comparable in IHx and NxC groups, but the epinephrine-induced [Hb] increase was larger in IHx. The alpha1- and alpha2-adrenoreceptor blockade (phentolamine) and alpha2-blockade (yohimbine) abolished the [Hb] increase of IHx rats. Conversely, alpha2-receptor stimulation (oxymetazoline) increased [Hb] during normoxia in IHx but not in NxC. In conclusion, this IHx protocol results in reversible [Hb] increases during hypoxia via splenic contraction mediated by increased alpha2-adrenoreceptor response. This may protect O2 supply during hypoxia without the cardiovascular burden of polycythemia during normoxia.

Adrenergic alpha-1 Receptor Agonists↗
PubMed1999

Effect of chronic sodium cyanate administration on O2 transport and uptake in hypoxic and normoxic exercise.

Systemic O2 transport during maximal exercise at different inspired PO2 (PIO2) values was studied in sodium cyanate-treated (CY) and nontreated (NT) rats. CY rats exhibited increased O2 affinity of Hb (exercise O2 half-saturation pressure of Hb = 27.5 vs. 42.5 Torr), elevated blood Hb concentration, pulmonary hypertension, blunted hypoxic pulmonary vasoconstriction, and normal ventilatory response to exercise. Maximal rate of convective O2 transport was higher and tissue O2 extraction was lower in CY than in NT rats. The relative magnitude of these opposing changes, which determined the net effect of cyanate on maximal O2 uptake (VO2 max), varied at different PIO2: VO2 max (ml. min-1. kg-1) was lower in normoxia (72.8 +/- 1.9 vs. 81. 1 +/- 1.2), the same at 70 Torr PIO2 (55.4 +/- 1.4 vs. 54.1 +/- 1.4), and higher at 55 Torr PIO2 (48 +/- 0.7 vs. 40.4 +/- 1.9) in CY than in NT rats. The beneficial effect of cyanate on VO2 max at 55 Torr PIO2 disappeared when Hb concentration was lowered to normal. It is concluded that the effect of cyanate on VO2 max depends on the relative changes in blood O2 convection and tissue O2 extraction, which vary at different PIO2. Although uptake of O2 by the blood in the lungs is enhanced by cyanate, its release at the tissues is limited, probably because of a reduction in the capillary-to-tissue PO2 diffusion gradient secondary to the increased O2 affinity of Hb.

Animals↗
PubMed1999

Hypoxia causes leukocyte adherence to mesenteric venules in nonacclimatized, but not in acclimatized, rats.

Although the effects of ischemia-reperfusion have received considerable attention, few studies have directly evaluated the microcirculatory response to systemic hypoxia. The overall objective of this study was to assess the effect of environmental hypoxia on adhesive interactions of circulating leukocytes with rat mesenteric venules by using intravital microscopy. Experiments were designed to 1) characterize the adhesive interactions of circulating leukocytes to venules during acute hypoxia produced by a reduction in inspired PO(2), 2) evaluate the role of nitric oxide in these adhesive interactions, 3) determine whether the effect of hypoxia on leukocyte adhesive interactions differs between acclimatized and nonacclimatized rats, and 4) assess whether compensatory changes in nitric oxide formation contribute to this difference. The results showed that acute hypoxia promotes leukocyte-endothelial adherence in mesenteric venules of nonacclimatized rats. The mechanism of this response is consistent with depletion of nitric oxide within the microcirculation. In contrast, no leukocyte-endothelial adherence occurred during hypoxia in rats acclimatized to hypobaric hypoxia. The results are consistent with increased nitric oxide formation due to expression of inducible nitric oxide synthase during the acclimatization period. Further studies are needed to establish the cause of nitric oxide depletion during acute hypoxia as well as to define the compensatory responses that attenuate hypoxia-induced leukocyte-endothelial adherence in the microvasculature of acclimatized rats.

Acclimatization↗
PubMed1999

Systemic hypoxia promotes leukocyte-endothelial adherence via reactive oxidant generation.

We recently demonstrated that systemic hypoxia during reduced inspired PO(2) produces a rapid increase in leukocyte adherence to rat mesenteric venules. Evidence suggests that the mechanism of this response involves decreased nitric oxide (NO) levels. One possible pathway for NO depletion could involve increased reactive oxygen species (ROS) generation resulting in inactivation of NO. The overall goal of the present study was to examine the role of ROS in promoting leukocyte-endothelial adherence during systemic hypoxia. Experiments were designed to 1) evaluate changes in ROS generation in the mesenteric microcirculation during systemic hypoxia, 2) determine how the ROS signal changes when PO(2) levels return to normal after a period of systemic hypoxia, 3) assess the effect of antioxidants on ROS generation during hypoxia, and 4) utilize antioxidants to examine the functional relationship between ROS generation and leukocyte adherence during hypoxia. The major findings from this study are that systemic hypoxia increases ROS generation within the mesenteric microcirculation and that antioxidants prevent the increase in leukocyte-endothelial adhesive interactions observed in hypoxia.

Animals↗
PubMed1998

Increasing maximal heart rate increases maximal O2 uptake in rats acclimatized to simulated altitude.

Maximal exercise heart rate (HRmax) is reduced after acclimatization to hypobaric hypoxia. The low HRmax contributes to reduce maximal cardiac output (Qmax) and may limit maximal O2 uptake (VO2max). The objective of these experiments was to test the hypothesis that the reduction in Qmax after acclimatization to hypoxia, due, in part, to the low HRmax, limits VO2max. If this hypothesis is correct, an increase in Qmax would result in a proportionate increase in VO2max. Rats acclimatized to hypobaric hypoxia [inspired PO2 (PIO2) = 69.8 +/- 3 Torr for 3 wk] exercised on a treadmill in hypoxic (PIO2 = 71.7 +/- 1.1 Torr) or normoxic conditions (PIO2 = 142.1 +/- 1.1 Torr). Each rat ran twice: in one bout the rat was allowed to reach its spontaneous HRmax, which was 505 +/- 7 and 501 +/- 5 beats/min in hypoxic and normoxic exercise, respectively; in the other exercise bout, HRmax was increased by 20% to the preacclimatization value of 600 beats/min by atrial pacing. This resulted in an approximately 10% increase in Qmax, since the increase in HRmax was offset by a 10% decrease in stroke volume, probably due to shortening of diastolic filling time. The increase in Qmax was accompanied by a proportionate increase in maximal rate of convective O2 delivery (Qmax x arterial O2 content), maximal work rate, and VO2max in hypoxic and normoxic exercise. The data show that increasing HRmax to preacclimatization levels increases VO2max, supporting the hypothesis that the low HRmax tends to limit VO2max after acclimatization to hypoxia.

Acclimatization↗
PubMed1997

Role of beta-adrenergic and cholinergic systems in acclimatization to hypoxia in the rat.

To role of beta-adrenergic and muscarinic cholinergic systems on maximal treadmill exercise performance and systemic O2 transport during hypoxic exercise (PIO2 approximately 70 Torr) was studied in rats acclimatized to hypobaric hypoxia (PIO2 approximately 70 Torr for 3 weeks, A rats) and in non-acclimatized littermates (NA rats). Untreated A rats had lower resting (fH) and maximal heart rate (fHmax) and cardiac output (Q), and higher maximal O2 uptake (VO2max) than NA. The only effect of cholinergic receptor blockade with atropine (Atp) was an increase in pre-exercise fH to comparable levels in A and in NA. beta 1-adrenergic receptor blockade with atenolol (Aten) lowered pre-exercise fH and (fHmax) to comparable values in A and in NA rats. However, since both pre-exercise fH and fHmax were lower in untreated A, the effect of Aten was relatively smaller in A. Aten reduced maximal exercise cardiac output (Qmax) in NA; however, tissue O2 extraction increased such that VO2max was not affected. Aten did not influence Qmax or any other parameter of systemic O2 transport in A. In conclusion the increased cholinergic tone may be responsible for the lower resting fH but not the lower fHmax of A; the integrity of the beta-adrenergic system is not necessary to attain VO2max in hypoxia either in A or in NA; the decreased response to beta-adrenergic stimulation in A limits the efficacy of this system on the mechanisms of systemic O2 transport and reduces the effect of its blockade on these mechanisms.

Acclimatization↗
PubMed1996

Chronic hypoxia decreases heterogeneity of pulmonary blood flow distribution in rats.

Pulmonary blood flow (PBF) distribution was studied in 15 chronically hypoxic rats (3 weeks, 10% O2 in N2) breathing 10% O2 (chronic hypoxia, CHx) and after 30 min of breathing air (acute normoxia, ANx). Controls were 15 normoxic littermates (normoxia, Nx) breathing air. Nonradioactive microspheres were infused into the inferior vena cava in the conscious resting state. The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). In Nx, PBF had a small but significant preferential distribution to the hilar, central regions, with lower blood flow to the peripheral regions (central-to-peripheral pattern). In CHx, however, there was no significant difference between blood flows to the central, middle and peripheral regions of the lung. ANx resulted in no change in PBF distribution. The results indicate that CHx attenuates the central-to-peripheral gradient of PBF distribution, probably due to vascular structural remodeling developed in CHx.

Animals↗
PubMed1995

Pulmonary blood flow distribution during acute hypoxia in conscious resting rats.

The effect of hypoxia on pulmonary blood flow (PBF) distribution were studied in 11 conscious resting rats. Microspheres were infused into the inferior vena cava during normoxia (Nx), acute normobaric hypoxia (AHx, 10% O2, 30 min), and 30 min after removal of hypoxia (post-hypoxia, PHx). The lungs were cut into 28 samples, and relative scatter of specific PBF was calculated as (sample activity/sample dry weight)/(total activity/total lung dry weight). Changes in pulmonary arterial pressure (PAP) during AHx were determined in five additional rats. During Nx, PBF was distributed preferentially to the hilar, central regions, rather than to the periphery. AHx resulted in a decrease in PaO2 from 85.1 +/- 0.9 to 37.8 +/- 1.2 Torr (mean +/- SE). Mean PAP increased significantly from 14.9 +/- 0.6 in Nx to 21.2 +/- 1.0 Torr in AHx (mean +/- SE). However, PBF distribution remained unchanged. PHx restored arterial blood gases and PAP to control levels without changing PBF distribution. The results indicate that conscious resting rats do not demonstrate changes in PBF distribution during AHx.

Animals↗
PubMed1995

Role of vasoconstrictors in the systemic hypertension of rats acclimatized to hypoxia.

Exposure to hypoxia (2-5 wk) results in systemic hypertension in rats and in humans. The possible mechanism(s) was investigated in rats acclimatized for 3 wk to barometric pressure of approximately 370 Torr (A) and in nonacclimatized littermates (NA) by administration of alpha-adrenergic [phentolamine (PHLM)], angiotensin II (ANG II), and arginine vasopressin (AVP V1) receptor antagonists. Both A and NA rats were studied in hypoxia (inspiratory O2 fraction = 0.10). Baseline mean arterial blood pressure (MABP) was higher in A than in NA rats: 126 +/- 4 vs. 101 +/- 2 mmHg (P < 0.05). Neither ANG II nor AVP V1 receptor antagonist influenced baseline MABP; however, both contributed to MABP recovery after PHLM. After simultaneous blockade of ANG II and AVP V1, PHLM lowered MABP by 65 +/- 2 and 45 +/- 3 mmHg in A and NA rats, respectively (P < 0.05). After combined blockade of the three systems, the smooth muscle relaxant sodium nitroprusside did not further modify MABP, which remained higher in A rats. It is concluded that 1) the hypertension in A rats is partly due to a higher alpha-adrenergic tone, 2) neither ANG II nor AVP contributes to the hypertension, but ANG II and AVP participate in MABP control after PHLM, 3) no other vasoconstrictor agents operate in either group, and 4) the higher MABP in A rats after sodium nitroprusside may reflect additional hypertensive mechanisms.

Acclimatization↗