Effects of chemoreceptor stimulation by almitrine bismesylate on renal function in conscious rats.
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Almitrine↗
Biomedical subjects
R Behm
Publications and source records attributed to R Behm.
Cardiovascular and renal effects of hypoxia in conscious carotid body-denervated rats.
The contribution of peripheral arterial chemoreceptors to cardiovascular and renal responses to acute hypocapnic hypoxia is currently not well understood. We compared the effects of normobaric hypoxia on mean arterial blood pressure (MABP), heart rate, glomerular filtration rate (GFR), renal blood flow (RBF), and renal volume and electrolyte excretion in conscious unilaterally nephrectomized carotid body-denervated (n = 10) and sham-operated (n = 10) control rats. Thirty minutes of normobaric hypoxia (12.5% O2) resulted in significant reductions in arterial PO2 and PCO2 as well as decreases in MABP, GFR, RBF, and renal sodium, potassium, and water excretion. These effects occurred more rapidly and/or were significantly more pronounced in carotid body-denervated than in sham-operated rats. These data indicate that moderate acute hypocapnic hypoxia has profound effects on systemic and renal hemodynamics as well as on renal excretory function in conscious rats. We conclude that stimulation of the peripheral arterial chemoreceptors can partially offset the hypoxia-induced decreases in MABP, RBF, GFR, urine flow, and urinary sodium and potassium excretion, thereby helping to maintain cardiovascular as well as fluid and electrolyte homeostasis.
Animals↗
Carotid chemoreceptors, systemic blood pressure, and chronic episodic hypoxia mimicking sleep apnea.
We have described a rat model that responds to repetitive episodic hypoxia (12-s infusions of nitrogen into daytime sleeping chambers every 30 s, 7 h/day for 35 days) with an increase in diurnal systemic blood pressure. We hypothesized that afferent information from the peripheral chemoreceptors may be necessary to produce diurnal blood pressure elevation in this hypoxia model. Carotid body denervation (CBD) was accomplished by severing both carotid sinus nerves in two groups of male Wistar rats (250-375 g). Group 4 CBD rats were subjected to intermittent hypoxia for 35 days (3-5% nadir ambient O2) as described above, whereas group 5 CBD rats remained unhandled in their usual cages. Additional sham-operated controls included group 2 sham-"hypoxia" rats, which were housed in chambers identical to the hypoxia rats but supplied with compressed air instead of nitrogen, group 1 (not denervated) rats, which remained unhandled in their usual cages, and group 3 sham-operated rats, which were subjected to 35 days of intermittent hypoxia identical to group 4 CBD rats. Femoral arterial baseline and end-of-study blood pressures were measured in conscious rats. The group 3 rats exposed to episodic hypoxia displayed a 13-mmHg increase in mean blood pressure, whereas the other groups showed no significant change from baseline. Left ventricular hypertrophy was evident in all rats exposed to episodic hypoxia, but right ventricular hypertrophy was evident only in the group 4 rats. All CBD rats developed increased hematocrit and hemoglobin, while the group 3 rats (non-CBD, episodic hypoxia) did not. The baroreceptor reflex at baseline was not depressed in the CBD rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Hyperoxia increases salt intake in spontaneously hypertensive rats (SHR).
The effect of normobaric hyperoxia on voluntary salt intake was investigated in 20 sham-operated and 11 carotid body-denervated SHR. While in sham-operated SHR the saline intake was enhanced during the whole hyperoxic period, the carotid body-denervated rats showed an increase in salt appetite only on the second and third day of hyperoxia. Water intake was not significantly different in sham-operated and carotid body-denervated SHR. These findings, together with our previous results, suggest that chemoreceptor activity determines salt appetite but not water intake in SHR.
Animals↗
Comparison of the effect of hypoxia on the secretion of the atrial natriuretic factor in spontaneously hypertensive and normotensive rats.
The effect of short lasting hypoxia on blood pressure, plasma atrial natriuretic peptide level and number of specific atrial granules were studied in 26 male spontaneously hypertensive and 24 normotensive Wistar rats. A great difference occurred in ANP secretion between hypertensive and normotensive rats. In the hypertensive animals elevated plasma ANP concentration (130 +/- 27 pg/ml) and decreased granularity in the right atria (73 +/- 2) were found on the first day of hypoxia with a slight elevation in urinary sodium content versus normotensive controls. The blood pressure also decreased although not significantly (190 +/- 14 mm Hg). In Wistar rats increased plasma ANP (130 +/- 34 pg/ml) and decreased atrial granularity versus normotensive controls (72 +/- 10 in the left and 113 +/- 16 in the right atrium) were observed only on the third day of hypoxia without changes in blood pressure and natriuresis. In SHR the rapid but short timed ANP release might be of right atrial origin and probably the consequence of a continuous and perhaps increased secretion of the peptide in normoxic conditions too. In Wistar rats the plasma ANP elevation could be secondary due to the increased plasma level of different vasoactive hormones to hypoxia. In the altered effect of ANP in hypertensive and normotensive hypoxic animals, structural and functional changes in the vascular bed may play a role.
Animals↗
Hypoxic modulation of systolic blood pressure and urinary sodium excretion in spontaneously hypertensive rats after carotid body denervation.
To explore the role of arterial chemoreceptors, the effect of hypobaric hypoxia on urinary sodium excretion and systolic blood pressure was investigated in conscious spontaneously hypertensive rats (SHR) with carotid body denervation (CBD) or after sham-operation (SO). Denervation of the carotid bodies was performed by section of the carotid sinus nerves. Exposure to hypobaric hypoxia equivalent to high altitude of 4000 m led to a more pronounced decrease in systolic blood pressure in CBD-rats than in SO-rats. The pattern of urinary sodium excretion observed on the first two days of hypoxia in both groups was not affected by the chemodenervation. It is being suggested that arterial chemoreceptors do not play a critical role in blood pressure and natriuretic responses to hypobaric hypoxia in conscious SHR.
Aldosterone↗
Effect of hypobaric hypoxia and almitrine on voluntary salt and water intake in carotid body denervated spontaneously hypertensive rats.
The effect of moderate hypobaric hypoxia and almitrine bismesylate (almitrine) on salt and water intake was investigated in carotid body denervated (CBD) and sham-operated (SO) spontaneously hypertensive rats (SHR). The animals were kept singly in metabolic cages and given free access to food, water and a 2.5% NaCl-solution. Oral administration of almitrine and exposure to hypobaric hypoxia for five days evoked a suppression of voluntary salt intake in SO-SHR, but not in CBD-SHR. Exposure of SO and CBD-SHR to hypobaric hypoxia resulted in a significant decrease in water intake in animals of both groups on the first day of hypoxia. Stimulation of the arterial chemoreceptors by almitrine induced no change in water intake similar to that evoked by hypobaric hypoxia. These results prove that stimulation of the arterial chemoreceptors has a direct effect on salt appetite but not on water intake in SHR.
Almitrine↗
Effect of chronic hypoxia on 45Ca and 86Rb uptake in aortic smooth muscle from spontaneously hypertensive rats (SHR).
The effect of chronic hypobaric hypoxia equivalent to a simulated high altitude of 4000 m was investigated on the Ca2+ and Rb+ uptake in vascular smooth muscle. The decline in systolic blood pressure in SHR due to hypoxia was associated with a significant decrease in 45Ca uptake and ouabain-insensitive 86Rb uptake as well as the tissue Ca2+ and K+ content. It seems likely that the reduction of the higher vascular tone in SHR by chronic hypoxia is due to the alteration of the transmembrane ion fluxes in the vascular smooth muscle cells. However, the meaning and the nature of the active and passive ion fluxes involved in this problem remains to be clarified.
Altitude↗
The paraganglia within the carotid bifurcation regions of young and old spontaneously hypertensive rats (SHR) after exposure to chronic hypobaric hypoxia. II. The carotid body-like organs.
The following paraganglia in the carotid bifurcations regions of spontaneously hypertensive rats (SHR) were studied: Endoneural paraganglia within the external carotid nerve, the carotid sinus nerve, the glossopharyngeal nerve, and the pharyngeal branch of the vagus nerve, the so-called periadventitial type I cells, and so-called miniglomera. Number and distribution of these paraganglia vary among different individuals. After chronically hypobaric hypoxia the volume of these paraganglia was increased but their number remained unchanged. The increase of volume was dependent on the duration of hypoxia. There were no differences between young and old SHR when the hypoxia-time was the same.
Animals↗
The paraganglia within the carotid bifurcation regions of young and old spontaneously hypertensive rats (SHR) after exposure to chronic hypobaric hypoxia. I. The carotid bodies.
Carotid body volumes and the histological appearance of these chemoreceptors were studied using light microscopic methods in 10 groups of spontaneously hypertensive rats (SHR). The aim of this study was to clarify the influence of chronic hypobaric hypoxia on the carotid bodies of SHR depending on the age of the rats, on the duration of exposure to hypoxia, and on different salt intake, respectively different blood pressure. We found that: 1. The carotid bodies of chronically hypoxic SHR are enlarged. 2. The degree of carotid body enlargement is dependent on the duration of exposure to hypoxia. 3. In old SHR the increase of carotid body volume was smaller than in young SHR. 4. Old chronically hypoxic SHR exhibited more distinct vascular changes in the carotid bodies than age-matched normoxic controls as well as younger chronically hypoxic and normoxic SHR. 5. The influence of different levels of systemic arterial blood pressure on the carotid body volumes was rather small compared with the effects of chronic hypobaric hypoxia.
Age Factors↗
Decrease of the salt appetite of spontaneously hypertensive rats by chronic application of almitrine.
The effect of almitrine on salt appetite, water intake, and renal excretory function was investigated in conscious adult spontaneously hypertensive rats (SHR) of both sexes. The animals were kept singly in metabolic cages and given free access to food, water and 2.5% NaCl-solution. Oral administration of almitrine (0.4 mg/kg) for five days evoked an effective long-lasting suppression of voluntary salt intake and a temporary decrease of water intake. The pattern of renal electrolyte excretion was determined by the pattern of intake. The present results support the assumption that the activity of the peripheral arterial chemoreceptors plays an essential role in the maintenance of voluntary salt intake in SHR.
Almitrine↗
Effect of almitrine on renal sodium excretion in chemoreceptor denervated spontaneously hypertensive rats.
The effect of almitrine on urinary sodium excretion was investigated in conscious carotid body-, sino-aortic- and sham-denervated SHR. The animals were kept singly in metabolic cages and had free access to food and tap water. Oral application of almitrine (0.5 mg/kg bwt) during five days induced a twofold natriuresis in sham-operated rats. The first natriuretic response on the fourth day of almitrine treatment was observed in animals of all groups indicating that this effect is not chemoreceptor mediated. The second natriuresis seen on the sixth day of the post-treatment period in both sino-aortic and sham-operated SHR but not in the carotid-body denervated rats does not permit clear conclusions to be drawn. We tend to assume that the natriuretic action of almitrine is not chemoreceptor mediated in conscious SHR.
Almitrine↗
Blood pressure, heart rate and arterial blood gas reactions to acute hypoxia in carotid body denervated spontaneously hypertensive rats.
The role of the peripheral arterial chemoreceptors in the reflex control of respiration and the cardiovascular systems was studied in spontaneously hypertensive rats (SHR). In carotid body denervated and in sham-operated control rats mean arterial blood pressure, heart rate, respiratory rate and arterial blood gases were measured under normoxic conditions and in acute normobaric hypoxia. Under normoxia the carotid body denervated SHR differ from the sham-operated ones only in significantly lowered arterial pO2 and pH and in significantly increased pCO2 values. The carotid body denervated SHR react to acute hypoxia with a significantly smaller increase in respiratory rate, a more pronounced fall in the arterial pO2 and a greater decrease in mean arterial blood pressure than the sham-operated control rats. Our results suggest that carotid body chemoreceptors in SHR are of great importance in regulating respiration but of secondary consequence regarding the reflex control of the cardiovascular system.
Animals↗
Blood volume and carotid body size responses in spontaneously hypertensive rats during chronic treatment with hypobaric hypoxia or almitrine bismesylate.
The influence of chronic stimulation of the peripheral arterial chemoreceptors on plasma and red cell volumes and on carotid body volume was studied in spontaneously hypertensive rats (SHR). The animals were exposed to chronic hypobaric hypoxia or a chronic treatment with almitrine bismesylate from the 17th to the 30th week of life. At the end of the experiment the plasma volume was significantly lower in chronic hypobaric and almitrine-treated animals; the red cell volume was significantly higher in chronic hypoxic SHR only. The carotid body volume was also higher only in chronic hypoxic animals. It can be concluded that long-term stimulation of the peripheral arterial chemoreceptors influences the adjustment of the plasma volume.
Adaptation, Physiological↗
Hypoxia-induced regression of adaptive structural microvessel reactions caused by long-term contraction influences in spontaneously hypertensive rats (SHR).
Chronic effects of hypobaric hypoxia (hb.h.) on the microcirculatory system (m.s.) of skeletal muscle were investigated. A new histomorphometric method was applied to detect the adaptive structural reactions of wall cells to long term changes in contraction performance. Seventeen SHR were exposed to hb.h. from 5 to 18 or 17 to 30 weeks of life, respectively. For controls 19 SHR and 25 normotensive Wistar rats were kept at sea level. The findings document long-term actions of vasorelaxation factors in hb.h. and the ability of the latter to antagonize the intensified vasocontraction factors in SHR. Depending on the stage of hypertension, there are different preferential sides for the actions of both these factors within the various districts of the m.s.
Adaptation, Physiological↗
The link between chemoreceptor activity and voluntary salt intake in spontaneously hypertensive rats: a hypothesis.
The effect of normobaric hyperoxia on voluntary salt intake was investigated in conscious male SHR (n = 16). The animals were housed individually in metabolic cages and given free access to food, water and 2.5% NaCl-solution. The exposure of the rats to 40% oxygen in nitrogen for four days resulted in a significant enhancement of the salt intake. The present experiment further clarifies the relationship between chemoreceptor activity and salt intake. Hypobaric hypoxia as well as the pharmacological substance almitrine, both stimuli of the carotid bodies, decrease the voluntary salt intake in SHR significantly, whereas hyperoxia, characterized by lowering of the chemoreceptor activity, increases the salt intake. Our studies support the hypothesis that chemoreceptor activity has a modulating influence on salt appetite in SHR.
Animals↗
Comparison of the response of renal sodium excretion to almitrine and hypoxia in conscious normotensive and spontaneously hypertensive rats.
The effect of hypobaric hypoxia and almitrine on renal sodium excretion and systolic blood pressure was investigated in conscious adult normotensive control rats (NCR) and spontaneously hypertensive rats (SHR). Moderate hypoxia caused a significant natriuresis within the first two days in both NCR and SHR. The systolic blood pressure was significantly diminished in SHR only. Oral application of almitrine (1.0 mg/kg b.w.) induced natriuresis in SHR and NCR. However, there are considerable differences in the pattern of natriuresis between the animals of both strains and when compared to the effect of hypoxia. The urinary sodium excretion by almitrine was not associated with a decrease in systolic blood pressure neither in SHR nor in NCR. The results indicate that both hypoxia and almitrine induce a strong natriuresis in conscious rats apparently by different mechanisms. However, there is no real evidence at present as to whether the peripheral arterial chemoreceptors are indeed involved in these mechanisms, or not, and if so, to what degree.
Almitrine↗
Almitrine bismesylate modulates the susceptibility of guinea pig pulmonary artery to catecholamines, PGF2 alpha and adenosine.
The action of almitrine bismesylate, a potent ventilatory stimulant drug, was studied on the contractile responses to some putative transmitters of carotid body (dopamine, noradrenaline, PGF2 alpha, adenosine) in segments of guinea pig pulmonary arteries. Almitrine (10 mumol/l) was capable of mitigating the contractions evoked by dopamine (0.3 mmol/l), noradrenaline (1 mumol/l) and PGF2 alpha (10 mumol/l) as well. In vessels precontracted with noradrenaline, almitrine (added to the nutrient solution of vessels before applying noradrenaline) potentiated the adenosine-induced initial contractile response without influencing the methylxanthine-sensitive relaxing effect of this purine nucleoside. In contrast, almitrine antagonized the adenosine-induced contraction when applied under precontracted state of arteries. It is supposed that the results presented here could provide some explanation for the variable action of almitrine on pulmonary circulation. On the other hand, these results could serve as a pharmacological basis for further studies of the almitrine action on isolated carotid bodies.
Adenosine↗