Reflex pressor response to gastric mechanical stimulation in rats

Neural and humoral mechanisms involved in the reflex pressor response during mechanical stimulation of the stomach of rats were investigated. The arterial blood pressure response was prevented by inhibition of alpha-adrenergic vasoconstriction using either an alpha-adrenergic blocker or a ganglionic blocker. In addition, there was a small decrease in the response after nephrectomy. However, there were no alterations in the response after beta-adrenergic blockade, bilateral adrenalectomy, inhibition of converting enzyme activity with enalapril or bilateral cervical vagus nerve transection. The heart rate was not modified after either intervention. After vagotomy the time of recovery of the basal blood pressure was significantly prolonged. It can be concluded that the blood pressure response to mechanical stimulation of the stomach wall is of neural rather than of humoral origin and mainly involves activation of alpha-adrenergic receptors. Vagal efferent pathways could be also involved.     

Canine renal vascular response to bilateral carotid occlusion during hypoxia

Chloralose-urethane anesthetized dogs were utilized to determine if hypoxemic potentiation of the baroreceptor-mediated increase in renal sympathetic nerve activity (RSNA) results in sufficient renal vascular vasoconstriction to reduce renal blood flow (RBF) during bilateral carotid occlusion (BCO). Additionally, hypercapnia and mechanical ventilation were randomly combined with hypoxemia during BCO to determine if further augmentation of renal vasoconstriction could be accomplished. BCO resulted in a similar increase in blood pressure (renal perfusion pressure) in all periods. RBF was not reduced significantly by BCO during any period even though renal vascular resistance was significantly increased by BCO during each period. When hypoxemia was combined with hypercapnia and mechanical ventilation simultaneously, there was a greater percentage increase in renal resistance with BCO. During BCO, when renal perfusion pressure was returned to control values by suprarenal aortic constriction, RBF remained unchanged and renal resistance decreased to control values. These results indicate that the BCO-induced increase in RSNA is relatively moderate and, even when potentiated by hypoxemia, hypercapnia, and mechanical ventilation, is not sufficient to reduce RBF in the presence of an increase in blood pressure and renal autoregulation.     

Increased pressor responses to pressor agents in spontaneously hypertensive rats.

Pressor reactivity to a variety of pressor agents after partial ganglionic blockade induced with hexamethonium was investigated in intact, in spinalized, and in chemically sympathectomized, spontaneously hypertensive rats (SHR). Responses of unanaesthetized 6-month-old SHR to noradrenaline, phenylephrine, and angiotensin after hexamethonium administration (32 mg/kg) markedly exceeded those of unanaesthetized, age-matched normotensive Wistar-Kyoto rats (WKR). Responses of anaesthetized SHR to noradrenaline after hexamethonium administration (16 mg/kg) were also increased at the hypertensive stages but not at the prehypertensive stages, when compared with those of anaesthetized normotensive Wistar rats of respective ages. In spinalized and chemically sympathectomized preparations after hexamethonium administration (16 mg/kg), noradrenaline produced equal increases in blood pressure in 6-month-old SHR and WKR. It is suggested that the functional sympathetic nervous system is important for the hyperreactivity of intact SHR.     

Ventilatory response to sustained hypoxia in carotid body denervated rats

Hypoxia stimulates ventilation, but when it is sustained, a decline in the ventilatory response is seen. The mechanism responsible for this decline lies within the CNS, but still remains unknown. In this study, we attempted to elucidate the possible role of hypoxia-induced depression of respiratory neurons by comparing the ventilatory response to hypoxia in intact rats and those with denervated carotid bodies. A whole-body plethysmograph was used to measure tidal volume, frequency of breathing and minute ventilation (VE) in awake and anesthetized intact rats and rats after carotid body denervation during exposure to hypoxia (FIO2 0.1). Fifteen-minute hypoxia induced an initial increase of VE in intact rats (to 248% of control ventilation in awake and to 227% in anesthetized rats) followed by a consistent decline (to 207% and 196% of control VE, respectively). Rats with denervated carotid bodies responded with a smaller increase in VE (to 134% in awake and 114% in anesthetized animals), but without a secondary decline (145% and 129% of control VE in the 15th min of hypoxia). These results suggest that afferentation from the carotid bodies and/or the substantial increase in ventilation are crucial for the biphasicity of the ventilatory response to sustained hypoxia and that a central hypoxic depression cannot fully explain the secondary decline in VE.     

Effect of naloxone on physostigmine-induced pressor response in adrenalectomized rats

Physostigmine-induced pressor response was studied in adrenalectomized rats. The increase in mean arterial blood pressure elicited by intravenous administration of physostigmine was not altered by adrenalectomy or sham-operation. The pressor response to intracerebroventricular administration of physostigmine was found to be partially inhibited in both acutely adrenalectomized and sham-operated rats, but not in those adrenalectomized 24 h earlier. This inhibition was completely prevented by naloxone pretreatment. The results suggest that endogenous opioid peptide release induced by surgical stress may be responsible for inhibition of the pressor effect of centrally administered physostigmine in rats.     

Increase in duration of paradoxical sleep after carotid occlusion in rats

Nonlinear rats, which survived after occlusion of one or two common carotid arteries (N = 30, about 30% survived) were examined. Sham-operated animals formed a control group. In animals with ischemia, the total sleep duration in a three-hour period was substantially increased as compared to control group at the expense of a substantial growth (8-9 times) of paradoxical sleep (PS) phase. In the animals with ischemia, a sharp increase in PS was observed on the first postoperation day, and then PS gradually decreased from the first to the fortieth days. The results suggest the PS involvement in the brain intrinsic reparation functions.     

Enhanced sympathoinhibitory response to volume expansion in conscious hindlimb-unloaded rats.

Prolonged exposure to microgravity or bed rest produces cardiovascular deconditioning, which is characterized by reductions in plasma volume, alterations in autonomic function, and a predisposition toward orthostatic intolerance. Although the precise mechanisms have not been fully elucidated, it is possible that augmented cardiopulmonary reflexes contribute to some of these effects. The purpose of the present study was to test the hypothesis that sympathoinhibitory responses to volume expansion are enhanced in the hindlimb-unloaded (HU) rat, a model of cardiovascular deconditioning. Mean arterial blood pressure, heart rate, and renal sympathetic nerve activity (RSNA) responses to isotonic volume expansion (0.9% saline iv, 15% of plasma volume over 5 min) were examined in conscious HU (14 days) and control animals. Volume expansion produced decreases in RSNA in both groups; however, this effect was significantly greater in HU rats (-46 +/- 7 vs. -25 +/- 4% in controls). Animals instrumented for central venous pressure (CVP) did not exhibit differences in CVP responses to volume expansion. These data suggest that enhanced cardiopulmonary reflexes may be involved in the maintenance of reduced plasma volume and contribute to attenuated baroreflex-mediated sympathoexcitation after spaceflight or bed rest.     

Conversion of brain angiotensin II to angiotensin III is critical for pressor response in rats

The present investigation measured the relative pressor potencies of intracerebroventricularly infused ANG II, ANG III, and the metabolically resistant analogs d-Asp(1)ANG II and d-Arg(1)ANG III in alert freely moving rats. The stability of these analogs was further facilitated by pretreatment with the specific aminopeptidase A inhibitor EC33 or the aminopeptidase N inhibitor PC18. The results indicate that the maximum elevations in mean arterial pressure (MAP) were very similar for each of these compounds across the dose range 1, 10, and 100 pmol/min during a 5-min infusion period. However, d-Asp(1)ANG II revealed significantly extended durations of pressor effects before return to base level MAP. Pretreatment intracerebroventricular infusion with EC33 blocked the pressor activity induced by the subsequent infusion of d-Asp(1)ANG II, whereas EC33 had no effect on the pressor response to subsequent infusion of d-Arg(1)ANG III. In contrast, pretreatment infusion with PC18 extended the duration of the d-Asp(1)ANG II pressor effect by about two to three times and the duration of d-Arg(1)ANG III's effect by approximately 10 to 15 times. Pretreatment with the specific AT(1) receptor antagonist losartan blocked the pressor responses induced by the subsequent infusion of both analogs indicating that they act via the AT(1) receptor subtype. These results suggest that the brain AT(1) receptor may be designed to preferentially respond to ANG III, and ANG III's importance as a centrally active ligand has been underestimated.     

Possible mechanisms of unilateral hippocampal insult after bilateral occlusion of common carotid arteries in rats with different types of behavior

Possible mechanisms of unilateral ischemic insults in CA1 region of hippocampus and anterior dorsal nuclei of thalamus after bilateral occlusion of common carotid arteries in rats with different types of behavior are discussed.     

Predictability and possible mechanisms of plankton response to reduction of planktivorous fish

The predictability of plankton response to reductions of planktivorous fish was investigated by comparing the plankton community in three biomanipulated lakes and ten unmanipulated lakes differing in intensity of fish predation. Data collected on total phosphorus, phytoplankton and zooplankton biomass and share of cyanobacteria and large grazers, as well as specific growth rate of phytoplankton, were further used to test some of the proposed underlying response-mechanisms. In the biomanipulated lakes the algal biomass and share of cyanobacteria decreased, specific growth rate of phytoplankton increased, and zooplankton biomass and share of large grazers increased or remained unchanged. This pattern was largely reflected in the differences in food-chain structure between the unmanipulated lakes with highversus those with low fish predation. The qualitative response to planktivorous fish reduction thus seems largely predictable. The biomanipulated lakes differed, however, in magnitude of response: the smallest hypertrophic, rotenone-treated lake (Helgetjern) showed the most dramatic response, whereas the large, deep mesotrophic lake (Gjersjøen), which was stocked with piscivorous fish, showed more moderate response, probably approaching a new steady state. These differences in response magnitude may be related to different perturbation intensity (rotenone-treatmentversus stocking with piscivores), food-chain complexity and trophic state. Both decreased phosphorus concentration and increased zooplankton grazing are probably important mechanisms underlying plankton response to biomanipulation in many lakes. The results provide tentative support to the hypothesis that under conditions of phosphorus limitation, increased zooplankton grazing can decrease algal biomassvia two separate mechanisms: reduction of the phosphorus pool in the phytoplankton, and reduction of the internal C:P-ratio in the phytoplankton cells.

     

Enhanced catabolism to acetaldehyde in rostral ventrolateral medullary neurons accounts for the pressor effect of ethanol in spontaneously hypertensive rats

We have previously shown that ethanol microinjection into the rostral ventrolateral medulla (RVLM) elicits sympathoexcitation and hypertension in conscious spontaneously hypertensive rats (SHRs) but not in Wistar-Kyoto (WKY) rats. In this study, evidence was sought to implicate the oxidative breakdown of ethanol in this strain-dependent hypertensive action of ethanol. Biochemical experiments revealed significantly higher catalase activity and similar aldehyde dehydrogenase (ALDH) activity in the RVLM of SHRs compared with WKY rats. We also investigated the influence of pharmacological inhibition of catalase (3-aminotriazole) or ALDH (cyanamide) on the cardiovascular effects of intra-RVLM ethanol or its metabolic product acetaldehyde in conscious rats. Compared with vehicle, ethanol (10 μg/rat) elicited a significant increase in blood pressure in SHRs that lasted for the 60-min observation period but had no effect on blood pressure in WKY rats. The first oxidation product, acetaldehyde, played a critical role in ethanol-evoked hypertension because 1) catalase inhibition (3-aminotriazole treatment) virtually abolished the ethanol-evoked pressor response in SHRs, 2) intra-RVLM acetaldehyde (2 μg/rat) reproduced the strain-dependent hypertensive effect of intra-RVLM ethanol, and 3) ALDH inhibition (cyanamide treatment) uncovered a pressor response to intra-RVLM acetaldehyde in WKY rats similar to the response observed in SHRs. These findings support the hypothesis that local production of acetaldehyde, due to enhanced catalase activity, in the RVLM mediates the ethanol-evoked pressor response in SHRs.     

VR-1 receptor blockade attenuates the pressor response to capsaicin but has no effect on the pressor response to contraction in cats

Vanilloid type 1 (VR-1) receptors are stimulated by capsaicin and hydrogen ions, the latter being a by-product of muscular contraction. We tested the hypothesis that activation of VR-1 receptors during static contraction contributes to the exercise pressor reflex. We established a dose of iodoresinaferatoxin (IRTX), a VR-1 receptor antagonist, that blocked the pressor response to capsaicin injected into the arterial supply of muscle. Specifically, in eight decerebrated cats, we compared pressor responses to capsaicin (10 mug) injected into the right popliteal artery, which was subsequently injected with IRTX (100 mug), with those to capsaicin injected into the left popliteal artery, which was not injected with IRTX. The pressor response to capsaicin injected into the right popliteal artery averaged 49 +/- 9 mmHg before IRTX and 9 +/- 2 mmHg after IRTX (P < 0.05). In contrast, the pressor response to capsaicin injected into the left popliteal artery averaged 46 +/- 10 mmHg before and 43 +/- 6 mmHg after (P > 0.05). We next determined whether VR-1 receptors mediated the pressor response to contraction of the triceps surae. During contraction without circulatory occlusion, the pressor response before IRTX (100 mug) averaged 26 +/- 3 mmHg, whereas it averaged 22 +/- 3 mmHg (P > 0.05) after IRTX (n = 8). In addition, during contraction with occlusion, the pressor responses averaged 35 +/- 3 mmHg before IRTX injection and 49 +/- 7 mmHg after IRTX injection (n = 7). We conclude that VR-1 receptors play little role in evoking the exercise pressor reflex.     

beta-Endorphin modulation of pressor response to hyperventilation in hypertensive patients

After hyperventilation, systolic and diastolic blood pressure (BP) significantly decreased in 14 hypertensive patients (group 1), did not change in 9 (group 2) and increased in 8 (group 3). Basal BP, norepinephrine and dynorphin B levels were higher in group 1 than in groups 2 and 3. The decrease in BP after hyperventilation was associated with a decrease in plasma norepinephrine, Met-enkephalin and dynorphin B and an increase in beta-endorphin. Naloxone abolished the hyperventilation-induced BP and norepinephrine decreases. Our findings indicate that hyperventilation may select hypertensive patients with different sympatho-adrenergic activity and that the increase in beta-endorphin reduces BP response to hyperventilation in patients with high sympatho-adrenergic tone.     

Dorsal root tetrodotoxin-resistant sodium channels do not contribute to the augmented exercise pressor reflex in rats with chronic femoral artery occlusion

We investigated the contribution of tetrodotoxin (TTX)-resistant sodium channels to the augmented exercise pressor reflex observed in decerebrated rats with femoral artery ligation. The pressor responses to static contraction, to tendon stretch, and to electrical stimulation of the tibial nerve were compared before and after blocking TTX-sensitive sodium channels on the L3-L6 dorsal roots of rats whose hindlimbs were freely perfused and rats whose femoral arteries were ligated 72 h before the start of the experiment. In the freely perfused group (n=9), pressor (Δ22±4 mmHg) and cardioaccelerator (Δ32±6 beats/min) responses to contraction were attenuated by 1 μM TTX (Δ4±1 mmHg, P<0.05 and Δ17±4 beats/min, P<0.05, respectively). In the 72 h ligated group (n=9), the augmented pressor response to contraction (32±4 mmHg) was also attenuated by 1 μM TTX (Δ8±2 mmHg, P<0.05). The cardioaccelerator response to contraction was not significantly attenuated in these rats. In addition, TTX suppressed the pressor response to tendon stretch in both groups of rats. Electrical stimulation of the tibial nerve evoked similar pressor responses between the two groups (freely perfused: Δ74±9 mmHg and 72 h ligated: Δ78±5 mmHg). TTX attenuated the pressor response to the tibial nerve stimulation by about one-half in both groups. Application of the TTX-resistant sodium channel blocker A-803467 (1 μM) with TTX (1 μM) did not block the pressor response to tibial nerve stimulation to any greater extent than did application of TTX (1 μM) alone. Although the contribution of TTX-resistant sodium channels to the augmented exercise pressor reflex may be slightly increased in rats with chronic femoral artery ligation, TTX-resistant sodium channels on dorsal roots do not play a major role in the augmented exercise pressor reflex.     

Similar poststimulatory pressor responses with different mechanisms in response to excitation of the locus coeruleus before and after acute adrenalectomy

Electrical stimulation of the locus coeruleus in anesthetized rats evoked a biphasic pressor response consisting of an initial sharp rise in blood pressure at the onset of stimulation, followed by a second elevation after cessation of the stimulus. This response, which was accompanied by an increase in plasma noradrenaline and adrenaline levels, was stable and could be easily reproduced over time. Sympathectomy by administration of guanethidine selectively abolished the primary pressor response. beta-Adrenergic blockade by intravenous administration of sotalol enhanced the secondary pressor response without affecting the primary component. Adrenal demedullation performed 24-48 h before the experiments selectively prevented the secondary pressor component. In contrast, acute adrenalectomy carried out during the experiment to impair the adrenomedullary secretions eliminated the secondary pressor response to stimulation of the locus coeruleus only in sympathectomized or in sotalol-treated rats but not in intact rats in which the response persisted. The latter, however, could be abolished by the administration of either guanethidine or sotalol, and it disappeared following repeated stimulation of the locus coeruleus. The study demonstrates that similar poststimulatory pressor responses with different underlying mechanisms can be elicited on excitation of the locus coeruleus before and after acute adrenalectomy in the rat. The results also suggest that intraneuronal adrenaline may be involved in the response evoked in acutely adrenalectomized animals.