Influence of the anteroventral third ventricle region and sinoaortic denervation on the pressor response to carotid occlusion.

The effect of anteroventral third ventricle (AV3V) lesion on the pressor response to occlusion of the common carotid artery was studied in freely moving rats with cuffs implanted 1 day before the tests. Short-term (6 hours) and long-term (2, 14, and 30 days) lesions greatly depressed the pressor responses to 60 seconds of common carotid occlusion. The initial peak, which depends on carotid innervation, was reduced by 55% (from 42 +/- 2 to 20 +/- 2 mm Hg), and the maintained response, which is of central origin (probably ischemic), was reduced by 32% (from 31 +/- 2 to 21 +/- 2 mm Hg). The effect of carotid or aortic denervation (or both) was also studied on control and lesioned rats. Carotid denervation produced similar extent of depression of the normal and reduced responses of the AV3V-lesioned rats 35% and 37%, respectively. Aortic denervation produced similar relative potentiation of the responses to common carotid occlusion of control and lesioned rats (72% and 66%, respectively). These data indicate the following: 1) Both short-term and long-term lesions greatly reduce the reflex and central (ischemic) components of the pressor responses to common carotid occlusion in freely moving rats; and 2) the importance of carotid innervation for development of the initial peak and the marked inhibitory effect of the aortic baroreceptor on both components are unchanged after AV3V lesion, when the depressed responses are evaluated as percent changes of the control values rather than as absolute changes.

Effect of testosterone on the pressor response to common carotid occlusion in gonadectomized conscious male rats with lesion of the median eminence.

The influence of testosterone on the development of the pressor response to common carotid occlusion was investigated in control and median eminence-lesioned male rats. In control rats (N = 9), gonadectomy performed 21 days before the experiments reduced by 22% (from 51 +/- 2 to 40 +/- 2 mmHg) and treatment with testosterone (300 micrograms for 4 days before the measurements) increased the initial peak pressor response (from 51 +/- 2 to 57 +/- 2 mmHg) which depends on carotid innervation. The maintained response which is of central origin (probably ischemic) was less affected. In nongonadectomized rats (N = 6), lesions of median eminence (6 days) decreased the initial peak by 19% (from 52 +/- 2 to 42 +/- 3 mmHg) and the maintained response by 56% (from 32 +/- 2 to 14 +/- 1 mmHg). Sham-operated rats served as controls. In gonadectomized animals (N = 6) the lesion reduced only the maintained response (from 23 +/- 2 to 11 +/- 1 mmHg). Testosterone supplementation restored the maintained response but did not alter the initial peak. These results indicate that the pressor response to common carotid occlusion in male rats is modulated by testosterone and that the depression in the maintained response caused by median eminence lesion can be reversed by steroid supplementation.

Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats.

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is of carotid reflex origin, was 40% greater in female than in male rats (45 +/- 2 vs 63 +/- 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 +/- 2 vs 37 +/- 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 +/- 2 mmHg) was similar to that of male rats (45 +/- 2 mmHg) but the late sustained response was 19% smaller (26 +/- 2 mmHg). Common carotid occlusion caused increases in heart rate which were greater in female (51 +/- 9 and 34 +/- 9 beats/min in the early pressor response and late sustained response, respectively) than in male rats (31 +/- 5 and 8 +/- 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 +/- 7 and 35 +/- 8 beats/min after 20s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure.

The effect of age on the pressor response produced by common carotid artery occlusion in conscious rats.

The pressor responses to 60 s of common carotid artery occlusion were studied in conscious male rats of different ages. Compared to rats at the age of 2 months, the initial peak and the maintained response in 6- 12- and 18-month old rats were well preserved. In 1-month old rats, both components were significantly depressed but in 24-month old rats only the initial peak of the pressor response was markedly attenuated. These findings demonstrate that age is an important factor in the response to common carotid artery occlusion which is more marked for the initial peak than the maintained response.

Influence of general anesthetics on baroreflex control of circulation.

1. The effects of sodium pentobarbital and alpha-chloralose anesthesia on the baroreflex control of circulation were studied in groups of 7 to 11 rats. The tests were performed in conscious undisturbed rats and repeated after anesthesia. 2. Pentobarbital (15 min) depressed the initial peak of the pressor response produced by carotid occlusion by 68% (15 +/- 1 vs 47 +/- 3 mmHg) and the maintained response by 52% (13 +/- 1 vs 27 +/- 4). Depression by chloralose was 48% (26 +/- 5 vs 50 +/- 3) and 21% (19 +/- 2 vs 24 +/- 3), respectively. The inhibition progressively declined at 30, 60, 90 and 120 min after pentobarbital but was unchanged up to 120 min after chloralose. 3. The baroreflex sensitivity index for bradycardic responses (phenylephrine injection) diminished by 50% after pentobarbital (-1.1 +/- 0.3 vs -2.2 +/- 0.3 beats/min per mmHg) and remained unaltered after chloralose. 4. The baroreflex sensitivity index for tachycardic responses (nitroprusside injection) was depressed by 61% after pentobarbital (-1.5 +/- 0.5 vs -3.8 +/- 0.5 beats/min per mmHg) and 35% after chloralose (-2.5 +/- 0.2 vs -3.9 +/- 0.5). 5. In general the depression of reflex control of circulation was more severe after pentobarbital than after chloralose anesthesia, while the resting control arterial pressure was not affected by either. The inhibition of the baroreflex tachycardic responses was more intense than that of the bradycardic responses and represented a better index of the depression exerted on the pressure responses to carotid occlusion.

Pressor responses to common carotid occlusion in female rats: effects of gonadectomy and treatment with gonadal steroid hormones.

The pressor responses to common carotid occlusion were studied in conscious female rats throughout the estrous cycle, after gonadectomy and after gonadectomy followed by treatment with estrogen and progesterone. The initial peak pressor response was highest during proestrus and fell significantly over the remaining 3 days of the estrous cycle. The maintained pressor response was relatively unchanged throughout the cycle, except during diestrus 1 when it decreased markedly. Gonadectomy reduced and treatment with estradiol alone increased the initial pressor component, respectively. Treatment of gonadectomized rats with estradiol plus progesterone enhanced both components. These findings suggest that gonadal steroid hormones are important modulators of the pressor response to common carotid occlusion.

Sex-related differences in the analgesic response to the rat tail immersion test.

The analgesic response was evaluated by the tail immersion test in adult male (N = 30), female (N = 21) and androgenized female Wistar rats (N = 15). The reaction time for tail withdrawal from the hot water bath was faster for male than for female rats (3.48 +/- 0.12 vs 6.46 +/- 0.42 s). The reaction time of androgenized female rats was similar to that of male rats (3.08 +/- 0.16 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) decreased the sensitivity to the noxious stimuli in males (4.08 +/- 0.10 s) and in androgenized females (3.69 +/- 0.19 s) but increased it in female rats (5.01 +/- 0.41 s). These data show sex-related differences in the analgesic response evaluated by the tail immersion test and indicate that administration of androgens to newborn female rats affects their pain sensitivity.

The role of opioids in the analgesic response of rats during the estrous cycle.

The analgesic response was evaluated by the tail immersion test in female rats during each phase of the estrous cycle. The reaction time (mean +/- SEM) for tail withdrawal from the hot water bath was faster during proestrus (5.78 +/- 0.28 s) and decreased significantly during estrus (5.31 +/- 0.30 s) and diestrus 1 (5.40 +/- 0.21 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) increased the sensitivity to the noxious stimulus only during proestrus (6.46 +/- 0.42 vs 5.02 +/- 0.41 s). These results suggest that the effects of gonadal steroids on nociception may involve an opioid pathway.

Participation of opioid receptors in the modulation of the analgesic response by adrenal and gonadal glands.

The involvement of opioid receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250 g). The reaction time (mean +/- SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 +/- 0.20 s) when compared to intact animals (6.09 +/- 0.23 s). Hormonal replacement with dexamethasone (50 micrograms/day) did not affect reaction time (3.38 +/- 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5 micrograms/day and progesterone 1.5 micrograms 6 h before the tests) therapy (5.11 +/- 0.45 s in animals treated with dexamethasone plus estradiol and 5.04 +/- 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2 mg/kg) decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 +/- 0.45 vs 4.15 +/- 0.44 s and 5.04 +/- 0.43 vs 3.87 +/- 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 +/- 0.18 vs 4.34 +/- 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones.

Effect of controlled ventilation on renal and splanchnic blood flows during severe arterial hypoxia.

The present study was undertaken to evaluate the extent that the lung inflation reflex attenuates vasoconstrictor responses in renal cortex and splanchnic beds during severe arterial hypoxia. Hypoxia was induced by inspiration of a 3-5% oxygen gas mixture in three groups of chloralose-anesthetized dogs: Group I, free breathing; Group II, controlled ventilation; Group III, free breathing with arterial PCO2 held constant. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In Group I, hypoxia caused marked hyperventilation, which was accompanied by no significant change in VC in renal cortex, and by reductions in VC in spleen (-36%), pancreas (-56%), and duodenum (-28%). In Group II, hypoxia caused reduction in VC in renal cortex (-70%), and reductions in VC in spleen, pancreas, and duodenum similar to those in Group I. In Group III, hypoxia again caused marked hyperventilation, but reductions in VC in renal cortex, spleen, pancreas, and duodenum were similar to those in Group II. Results indicate that during severe arterial hypoxia activation of lung inflation reflex does not attenuate or reverse vasoconstriction in renal cortex, spleen, pancreas, and duodenum.

Regional blood flow in canine brain during nicotine infusion: pentobarbital vs. chloralose anesthesia.

We compared vasoactive effects of intravenous nicotine (36 micrograms/kg/min) in regional cerebral circulations under pentobarbital and chloralose anesthesia. Experiments were conducted in three groups of dogs: Group I, pentobarbital anesthesia with fixed ventilation; Group II, chloralose anesthesia with fixed ventilation; Group III, chloralose anesthesia with free breathing. Values for regional cerebral blood flow measured with 15 mu radioactive microspheres were used to compute regional cerebral vascular resistance (rCBR). In Group I, nicotine had no effect on rCVR in cerebral cortex, and it increased significantly rCVR in cerebellum (+17%), pons (+13%), medulla (+23%), and spinal cord (+19%). Using chloralose instead of pentobarbital in dogs with fixed ventilation (Group II), caused a significant reduction in rCVR in the cerebral cortex during nicotine, although it did not alter significantly nicotine-induced changes in rCVR in other regions of the brain. Hypocapnic alkalosis during nicotine-induced hyperventilation (Group III) resulted in significant increases in rCVR in all regions of the brain; however, the increases in rCVR in non-cortical regions more than doubled those in the cerebral cortex. The present results indicate: Nicotine-induced vasodilation in cerebral cortex was blunted by pentobarbital anesthesia. Nicotine-induced vasodilation in cerebral cortex under chloralose anesthesia was sufficient to nullify in part the potent vasoconstrictor effect of hypocapnic alkalosis.

Regional hemodynamic responses to nicotine in conscious and anesthetized dogs: comparative effects of pentobarbital and chloralose.

This study was conducted in 12 dogs to evaluate regional hemodynamic responses during intravenous infusion of nicotine (36 micrograms/kg/min) in the conscious state and compare them with those in the same dogs following either pentobarbital (n = 6) or chloralose anesthesia (n = 6). Values for regional blood flow were obtained with 15-microns radioactive microspheres and used to calculate regional vascular conductance. In the conscious state, nicotine increased aortic pressure (+70%) and caused hyperventilation that reduced arterial PCO2 (-44%). These systemic effects were associated with decreases in vascular conductance in the renal cortex (-48%), pancreas (-81%), duodenum (-58%), and cerebral cortex (-55%), whereas no significant change in vascular conductance was evident in spleen, liver, or myocardium. Pentobarbital anesthesia blunted the increases in aortic pressure and respiratory activity and the reductions in vascular conductance in the renal cortex, pancreas, duodenum, and cerebral cortex during nicotine infusion. In contrast, chloralose anesthesia accentuated the increase in aortic pressure and the decrease in vascular conductance in the renal cortex during nicotine infusion, while it converted no change in vascular conductance in the spleen into a decrease and no change in vascular conductance in the myocardium into an increase. Chloralose anesthesia blunted nicotine-induced hyperventilation. These findings demonstrate that general anesthetic agents may have markedly different effects on cardiovascular reflex pathways. They emphasize the importance of considering the particular characteristics of the anesthetic agent used in interpreting results from studies of cardiovascular pharmacology and physiology in anesthetized animals.

Effect of controlled ventilation on renal and splanchnic blood flows during nicotine.

The present study was undertaken to evaluate the influence of respiratory condition [free breathing (FB) vs. controlled ventilation (CV)] and of anesthetic [pentobarbital (PA) vs. chloralose (CA)] on nicotine-induced vasomotor responses in the renal cortex and splanchnic beds. Nicotine (36 micrograms . kg-1 . min-1 iv) was infused in four groups of dogs: group I, PA and CV; group II, PA and FB; group III, CA and CV; group IV, CA and FB. Regional vascular conductances (VC) were calculated from regional blood flows measured with 15-microns radioactive microspheres. In group I, VC fell in renal cortex (-22%) and pancreas (-52%), increased in liver (hepatic arterial bed +130%), and did not change significantly in duodenum and spleen. In group III, VC fell to a greater extent in renal cortex, pancreas, duodenum, and spleen than in group I; VC in hepatic arterial bed did not change. In FB dogs (groups II and IV), nicotine caused marked hyperventilation, but decreases in VC in renal cortex, pancreas, and duodenum were similar to those in CV dogs. Results indicate that during intravenous infusion of nicotine 1) hyperventilation does not attenuate or reverse vasoconstriction in renal cortex, pancreas, or duodenum under either PA or CA, although it does in spleen under CA; 2) vasodilator mechanisms predominate over vasoconstrictor mechanisms in the hepatic arterial bed; and 3) vasoconstrictor responses in renal cortex, pancreas, duodenum, spleen, and liver are more pronounced under CA than under PA.

Sex-related differences in the analgesic response to the rat tail immersion test

The analgesic response was evaluated by the tail immersion test in adult male (N = 30), female (N = 21) and androgenized female Wistar rats (N = 15). The reaction time for tail withdrawal from the hot water bath was faster for male than for female rats (3.48 +/- 0.12 vs 6.46 +/- 0.42 s). The reaction time of androgenized female rats was similar to that of male rats (3.08 +/- 0.16 s). Blockade of opiate receptors with naloxone (2 mg/kg, ip) decreased the sensitivity to the noxious stimuli in males (4.08 +/- 0.10 s) and in androgenized females (3.69 +/- 0.19 s) but increased it in female rats (5.01 +/- 0.41 s). These data show sex-related differences in the analgesic response evaluated by the tail immersion test and indicate that administration of androgens to newborn female rats affects their pain sensitivity.

Sex-related differences in cardiovascular responses to common carotid occlusion in conscious rats

Mean arterial pressure and heart rate were determined in conscious, unrestrained groups of 10 male, female and androgenized female Wistar rats 20 s (early pressor response) and 1 min (late sustained response) after bilateral carotid artery occlusion. The early pressor response, which is carotid reflex origin, was 40% greater in female than in male rats (45 ñ 2 vs 63 ñ 3 mmHg, respectively). The late sustained response, which is of central origin (probably ischemic), did not differ between male and female rats (32 ñ 2 vs 37 ñ 4 mmHg, respectively). The magnitude of the early pressor response of androgenized female rats (50 ñ 2 mmHg) was similar to that of male rats (45 ñ 2 mmHg) but the late sustained response was 19% smaller (26 ñ 2 mmHg). Common carotid occlusion caused increases in haert rate which were greater in female (51 ñ 9 and 34 ñ 9 beats/min in the early pressor response and late sustained response respectively) than in male rats (31 ñ 5 and 8 ñ 4 beats/min, respectively). In androgenized female rats, heart rate decreased during common carotid occlusion (34 ñ 7 and 35 ñ 8 beats/min after 20 s and 1 min, respectively). These data provide evidence that there are substantial sex-related differences in the cardiovascular responses to common carotid occlusion in conscoious rats and indicate that administration of androgens to newborn female rats affects the baroreceptor reflex control of their arterial pressure

Participation of opioid receptors in the modulation of the analgesic response by adrenal and gonadal glands

The invovlement of opiodi receptors in the analgesic response was evaluated by the tail-immersion test in simultaneously adrenalectomized and ovariectomized female Wistar rats (210-250g). The reaction time (mean ñ SEM) for tail withdrawal from hot water decreased significantly 2 weeks after surgery (3.52 ñ 0.20 s) when compared to intact animals (6.09 ñ 0.23 s). Hormonal replacement with dexamethasone (50*/day) did not affect reaction time (3.38 ñ 0.19 s). However, this response was restored by combined adrenal and gonadal steroid substitution (estradiol 5*g/day and progesterone 1.5*g 6h before the test) therapy (5.11 ñ 0.45 s) in animal treated with dexamethasone plus estradiol and 5.04 ñ 0.43 s in animals treated with dexamethasone plus estradiol plus progesterone). Naloxone (2mg/Kg decreased the reaction time of animals treated with adrenal and gonadal steroids (5.11 ñ 0.45 vs 4.15 ñ 0.44 and 5.04 ñ 0.43 vs 3.87 ñ 0.28 s, respectively, before and after naloxone) but failed to decrease it in rats treated with dexamethasone only (3.88 ñ 0.18 vs 4.34 ñ 0.25 s, before and after naloxone). These observations indicate that gonadal steroids are the most important steroid factors involved in the reaction time to tail immersion in hot water and confirm other reports that the opioid pathways modulating the neuronal circuitry require the presence of these hormones