In the parvocellular part of paraventricular nucleus, glutamatergic and GABAergic neurons mediate cardiovascular responses to AngII.

Angiotensinergic, GABAergic, and glutamatergic neurons are present in the parvocellular region of the paraventricular nucleus (PVNp). It has been shown that microinjection of AngII into the PVNp increases arterial pressure (AP) and heart rate (HR). The presence of synapses between the angiotensinergic, GABAergic, and glutamatergic neurons has been shown in the PVNp. In this study, we investigated the possible interaction between these three systems of the PVNp for control of AP and HR. All drugs were bilaterally (100 nl/side) microinjected into the PVNp of urethane-anesthetized rats, and AP and HR were recorded continuously. Microinjection of AngII into the PVNp produced pressor and tachycardia responses. Pretreatment of PVNp with AP5 or CNQX, glutamatergic NMDA and AMPA receptors antagonists, attenuated the responses to AngII. Pretreatment of PVNp with bicuculline greatly attenuated the pressor and tachycardia responses to AngII. In conclusion, this study provides the first evidence that pressor and tachycardia responses to microinjection of AngII into the PVNp are partly mediated by both NMDA and non-NMDA receptors of glutamate. Activation of glutamatergic neurons by AngII stimulates the sympathoexcitatory neurons. We also showed that the responses to AngII were strongly mediated by GABAA receptors, probably through activation of GABAergic neurons, which in turn inhibit sympathoinhibitory neurons.

Hypothalamic paraventricular nucleus augments baroreflex sensitivity, role of angiotensin II.

The hypothalamic paraventricular nucleus (PVN) is an important brain region involved in control of the cardiovascular system. Direct injection of angiotensin II (AngII) into the PVN produces a short or long pressor response. This study was performed in anesthetized rats to find whether the parvocellular part of the paraventricular nucleus (PVNp) affects the baroreflex. And if so, what is the effect of AngII injected into the PVNp on the baroreflex? Drugs were microinjected into the PVNp while blood pressure and heart rate were recorded continuously. We found that microinjection of AT1 and AT2 receptor antagonists into the PVNp region did not affect the baseline mean arterial pressure (MAP) and heart rate (HR) indicating that under normal conditions AngII may not provide tonic activity, at least in anaesthetized animals. Bilateral microinjections of a synaptic blocker (CoCl2) into the PVNp attenuated the baroreflex gains in responses to loading and unloading of baroreceptors, indicating that PVNp is involved in the baroreflex rate component. Microinjection of AngII into the PVNp increased MAP and HR. However, AngII slightly attenuated the baroreflex rate component using its two receptors AT1 and AT2. Collectively, these findings suggest that the PVNp as a whole is involved in the baroreflex. But AngII attenuates the heart rate response of the baroreflex through AT1 and AT2 receptors.

Another controller system for arterial pressure. AngII-vasopressin neural network of the parvocellular paraventricular nucleus may regulate arterial pressure during hypotension.

Angiotensin II (AngII) immunoreactive cells, fibers and receptors, were found in the parvocelluar region of paraventricular nucleus (PVNp) and AngII receptors are present on vasopressinergic neurons. However, the mechanism by which vasopressin (AVP) and AngII may interact to regulate arterial pressure is not known. Thus, we tested the cardiovascular effects of blockade of the AngII receptors on AVP neurons and blockade of vasopressin V1a receptors on AngII neurons. We also explored whether the PVNp vasopressin plays a regulatory role during hypotension in anesthetized rat or not. Hypovolemic-hypotension was induced by gradual bleeding from femoral venous catheter. Either AngII or AVP injected into the PVNp produced pressor and tachycardia responses. The responses to AngII were blocked by V1a receptor antagonist. The responses to AVP were partially attenuated by AT1 antagonist and greatly attenuated by AT2 antagonist. Hemorrhage augmented the pressor response to AVP, indicating that during hemorrhage, sensitivity of PVNp to vasopressin was increased. By hemorrhagic-hypotension and bilateral blockade of V1a receptors of the PVNp, we found that vasopressinergic neurons of the PVNp regulate arterial pressure towards normal during hypotension. Taken together these findings and our previous findings about angII (Khanmoradi and Nasimi, 2017a) for the first time, we found that a mutual cooperative system of angiotensinergic and vasopressinergic neurons in the PVNp is a major regulatory controller of the cardiovascular system during hypotension.

Roles of glutamate and GABA of the Kölliker-Fuse nucleus in generating the cardiovascular chemoreflex.

The Kölliker-Fuse (KF) nucleus is a part of the parabrachial complex, located in the dorsolateral pons. It is involved in the chemoreflex-evoked cardiovascular and respiratory changes, but the role of GABA and glutamate in cardiovascular chemoreflex has not been shown yet. This study was performed to determine the role of GABA, glutamate, and their interaction in the KF, in cardiovascular chemoreflex in anesthetized rat. The antagonists were microinjected into the KF, and arterial pressure, heart rate, and single-unit responses were recorded simultaneously. The chemoreflex was evoked by i.v. injection of KCN, consisted of a short pressor followed by long bradycardia responses. Both responses were significantly attenuated by injection of a synaptic blocker (CoCl2) into the KF, confirming involvement of the KF in generating the reflex. Microinjection of AP5, an NMDA receptor antagonist, into the KF significantly attenuated the pressor and bradycardia responses, while blocking the AMPA receptors by CNQX had no significant effect. Blockade of GABAA receptors by bicuculline methiodide (BMI) potentiated both responses. Co-injection of BMI and CNQX potentiated the responses too. Co-injection of BMI and AP5 had no significant effect on the pressor response but significantly attenuated the bradycardia response. In conclusion, the KF plays a role in generating cardiovascular chemoreflex via its glutamate NMDA but not AMPA receptors. GABA inhibits both components of this reflex through GABAA receptors. There is an interaction between GABAA and NMDA receptors in regulating the bradycardia response of the reflex. Single-unit results were also presented which were correlated with and supported the homodynamic findings.

The neurological manifestations of COVID-19: a review article.

RESULTS: Various neurological manifestations have been reported in the literature associated with COVID-19, which in the current study are classified into Central Nervous System (CNS) related manifestations including headache, dizziness, impaired consciousness, acute cerebrovascular disease, epilepsy, and Peripheral Nervous System (PNS) related manifestations such as hyposmia/anosmia, hypogeusia/ageusia, muscle pain, and Guillain-Barre syndrome. CONCLUSION: During the current context of COVID-19 pandemic, physicians should be aware of wide spectrum of neurological COVID-19 sign and symptoms for early diagnosis and isolation of patients. In this regard, COVID-19 has been associated with many neurological manifestations such as confusion, anosmia, and ageusia. Also, various evidences support the possible CNS roles in the COVID-19 pathophysiology. In this regard, further investigation of CNS involvement of SARS-COV-2 is suggested.

Functions of AT1 and AT2 angiotensin receptors in the paraventricular nucleus of the rat, correlating single-unit and cardiovascular responses.

The paraventricular hypothalamic nucleus (PVN) is a complex structure with both neuroendocrine and autonomic functions including cardiovascular control. The PVN contains angiotensin II (AngII) immunoreactive cells, fibers, as well as AT1 and AT2 receptors of AngII. We microinjected AngII into the PVN of normotensive anesthetized rats and simultaneously recorded blood pressure, heart rate (HR) and single-unit responses. The roles of AT1 and AT2 receptors in these responses were also evaluated. Microinjection of AngII into the PVN produced a short excitatory single-unit response and two types of pressor responses: short duration with a decrease in HR and long with an increase in HR. Microinjection of losartan, an AT1 antagonist, into the PVN produced two response types, attenuation and augmentation of the pressor and firing rate responses to AngII. Microinjection of PD123319, an AT2 antagonist, into the PVN greatly attenuated pressor and single-unit response to AngII, indicating that the pressor response was mediated through AT2 receptors too. In conclusion, microinjection of AngII into the PVN stimulates neurons resulting in an increase in firing rate and consequently produces a short or long pressor response. These responses were mediated through AT1 and AT2 receptors; however, AT1 receptor may produce inhibition too. The results suggest that AngII of the PVN may be a neurotransmitter playing a role in arterial pressure regulation.

Interaction of GABA and norepinephrine in the lateral division of the bed nucleus of the stria terminals in anesthetized rat, correlating single-unit and cardiovascular responses.

The bed nucleus of the stria terminalis (BST) consists of multiple anatomically distinct nuclei. The lateral division, which receives dense noradrenergic innervation, has been implicated in cardiovascular regulation and modulation of responses to stress. This study is performed to identify the cardiovascular and single-unit responses of the lateral BST to norepinephrine (NE), involved adrenoceptors, and possible interaction with GABAergic system of the BST in urethane-anesthetized rats. NE, adrenoreceptor antagonists, and GABAA antagonist were microinjected into the lateral division of BST, while arterial pressure (AP), heart rate (HR), and single-unit responses were simultaneously recorded. NE microinjected into the lateral division of BST produced depressor and bradycardic responses. The decrease in AP and HR to NE was blocked by prazosin, an α1-adrenoreceptor antagonist, but not by yohimbine, an α2 antagonist. Furthermore, injections of the GABAA receptor antagonist, bicuculline methiodide (BMI), into the lateral BST abolished the NE-induced depressor and bradycardic responses. We also observed single-unit responses consisting of excitatory and inhibitory responses correlated with cardiovascular function to the microinjection of NE. In conclusion, these data provide the first evidence that microinjection of NE in the lateral division of BST produces depressor and bradycardic responses in urethane-anesthetized rat. The depressor and bradycardiac response are mediated by local α1- but not α2-adrenoceptors. α1-AR activates the GABAergic system within the BST, which in turn produces depressor and bradycardic responses.

Endogenous angiotensin II in the paraventricular nucleus regulates arterial pressure during hypotension in rat, a single-unit study.

The hypothalamic paraventricular nucleus (PVN) controls cardiovascular regulation through vasopressin and sympathetic system. The PVN contains angiotensin II (AngII) and AngII receptors. We have already shown that microinjection of AngII into PVN produced a pressor response concomitant with an increase in firing rate of some PVN neurons. This study was performed to find if PVN AngII plays a regulatory function during hypotension. Hypovolemic-hypotension was induced and the possible role of the PVN AngII in returning arterial pressure toward normal was assessed by monitoring cardiovascular response and single-unit activity of the PVN neurons. Hemorrhage augmented the pressor, tachycardic and single-unit responses to AngII. After-hemorrhage injection of PD123319, an AT2 antagonist, into PVN resulted in a significant decrease in firing rate of some neurons, indicating that AngII was released into the PVN due to hemorrhage. Using single-unit recording, we found that PVN receives electrical signals from baroreceptors and from circulating AngII through circumventricular organs. In addition, by producing hemorrhagic-hypotension and bilateral blockade of AT2 receptors of the PVN, we found that AngII regulates arterial pressure toward normal during hypotension. So for the first time, it was verified that brain renin-angiotensin system is also a major regulatory system of the cardiovascular system.

Contribution of amygdala to the pressor response elicited by microinjection of angiotensin II into the bed nucleus of the stria terminalis.

The bed nucleus of the stria terminalis (BST) is part of the limbic system located in the rostral forebrain. BST is involved in behavioral, neuroendocrine and autonomic functions, including cardiovascular regulation. The amygdala, plays an important role in mediating the behavioral and physiological responses associated with fear and anxiety, including cardiovascular responses. In a previous study, we showed that microinjection of AngII into the BST produced a pressor and two types of single-unit responses in the BST, short excitatory and long inhibitory. This study was performed to find possible involvement of amygdala in cardiovascular responses elicited by microinjection of AngII into the BST, using blockade of the central nucleus of amygdala (CeA) and single unit recording from the CeA, while injecting AngII into the BST in anesthetized rat. Blockade of CeA attenuated the pressor response to microinjection of AngII into the BST. Eighty-six AngII microinjections were given into the BST and 198 single unit responses were recorded from CeA simultaneously, from which 89 showed a short duration excitatory response and 109 showed no responses. In conclusion, microinjection of AngII into the BST produces a short excitatory single unit response in the CeA, resulting in contribution of amygdala to the resulted pressor response. Taken together, our study and previous studies suggest a plausible hypothesis that these two nuclei perform their cardiovascular functions in cooperation with each other.

Angiotensin II in the paraventricular nucleus stimulates sympathetic outflow to the cardiovascular system and make vasopressin release in rat.

The hypothalamic paraventricular nucleus (PVN) plays essential roles in neuroendocrine and autonomic functions, including cardiovascular regulation. It was shown that microinjection of angiotensin II (AngII) into the PVN produced a pressor response. In this study, we explored the probable mechanisms of this pressor response. AngII was microinjected into the PVN and cardiovascular responses were recorded. Then, the responses were re-tested after systemic injection of a ganglionic blocker, Hexamethonium, or a vasopressin V1 receptor blocker. Hexamethonium pretreatment (i.v.) greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that the sympathetic system is involved in the cardiovascular effect of AngII in the PVN. Systemic pretreatment (i.v.) with V1 antagonist greatly and significantly attenuated the pressor response to AngII, with no significant effect on heart rate, indicating that vasopressin release is involved in the cardiovascular effect of AngII in the PVN. Overall, we found that AngII microinjected into the PVN produced a pressor response mediated by the sympathetic system and vasopressin release, indicating that other than circulating AngII, endogenous AngII of the PVN increases the vasopressin release from the PVN.

Vasopressin and sympathetic system mediate the cardiovascular effects of the angiotensin II in the bed nucleus of the stria terminalis in rat.

The bed nucleus of the stria terminalis (BST) is involved in cardiovascular regulation. The angiotensin II (Ang II) receptor (AT1), and angiotensinogen were found in the BST. In our previous study we found that microinjection of Ang II into the BST produced a pressor response. This study was performed to find the mechanisms mediating this response in anesthetized rats. Ang II was microinjected into the BST and the cardiovascular responses were re-tested after systemic injection of a blocker of autonomic or vasopressin V1 receptor. The ganglionic nicotinic receptor blocker, hexamethonium dichloride, attenuated the pressor response to Ang II, indicating that the cardiovascular sympathetic system is involved in the pressor effect of Ang II. A selective vasopressin V1 receptor antagonist greatly attenuated the pressor effect of Ang II, indicating that the Ang II increases the arterial pressure via stimulation of vasopressin release as well. In conclusion, in the BST, Ang II as a neurotransmitter increases blood pressure by exciting cardiovascular sympathetic system and directly or indirectly causing vasopressin to release into bloodstream by VPN. This is an interesting new finding that not only circulating Ang II but also brain Ang II makes vasopressin release.

GABA modulates baroreflex in the ventral tegmental area in rat.

There are some reports demonstrating the cardiovascular functions of the ventral tegmental area (VTA). About 20-30% of the VTA neurons are GABAergic, which might play a role in baroreflex modulation. This study was performed to find the effects of GABA(A), GABA(B) receptors and reversible synaptic blockade of the VTA on baroreflex. Drugs were microinjected into the VTA of urethane anesthetized rats, and the maximum change of blood pressure and the gain of the reflex bradycardia in response to intravenous phenylephrine (Phe) injection were compared with the preinjection and the control values. Microinjection of bicuculline methiodide (BMI, 100 pmol/100 nl), a GABA(A) antagonist, into the VTA strongly decreased the Phe-induced hypertension, indicating that GABA itself attenuated the baroreflex. Muscimol, a GABA(A) agonist (30 mM, 100 nl), produced no significant changes. Baclofen, a GABA(B) receptor agonist (1000 pmole/100 nl), moderately attenuated the baroreflex, however phaclofen, a GABA(B) receptor antagonist (1000 pmole/100 nl), had no significant effect. In conclusion, for the first time, we demonstrated that GABA(A) receptors of the VTA strongly attenuate and GABA(B) receptors of the VTA moderately attenuate baroreflex in rat.

Mechanism of the cardiovascular effects of the GABAA receptors of the ventral tegmental area of the rat brain.

The ventral tegmental area (VTA) contains GABA terminals involved in the regulation of the cardiovascular system. Previously, we demonstrated that blocking GABAA but not GABAB receptors produced a pressor response accompanied by marked bradycardia. This study was performed to find the possible mechanisms involved in these responses by blocking ganglionic nicotinic receptors, peripheral muscarinic receptors or peripheral V1 vasopressin receptors. Experiments were performed on urethane anesthetized male Wistar rats. Drugs were microinjected unilaterally into the VTA (100 nl). The average changes in mean arterial pressure (MAP) and heart rate (HR) were compared between pre- and post-treatment using paired t-test. Injection of bicuculline methiodide (BMI), a GABAA antagonist, into the VTA caused a significant increase in MAP and a decrease in HR. Administration (i.v.) of the nicotinic receptor blocker, hexamethonium, enhanced the pressor response but abolished the bradycardic response to BMI, which ruled out involvement of the sympathetic nervous system. Blockade of the peripheral muscarinic receptors by homatropine (i.v.) abolished the bradycardic effect of BMI, but had no effect on the pressor response, indicating that bradycardia was produced by the parasympathetic outflow to the heart. Both the pressor and bradycardic responses to BMI were blocked by V1 receptor antagonist (i.v.), indicating that administration of BMI in the VTA disinhibited the release of vasopressin into the circulation. In conclusion, we demonstrated that GABAergic mechanism of the VTA exerts a tonic inhibition on vasopressin release through activation of GABAA receptors. The sympathetic system is not involved in the decrease of blood pressure by GABA of the VTA.

Cardiovascular responses of the anterior claustrum; its mechanism; contribution of medial prefrontal cortex.

The anterior claustrum (CLa) has bilateral connections with the areas involved in cardiovascular regulation, though its role in cardiovascular control is not yet understood. This study was performed to find the cardiovascular responsive region of the CLa by stimulating all parts of the CLa with l-glutamate, and to find the possible mechanisms mediating its responses in urethane-anesthetized rats. We also investigated the possible involvement of the medial prefrontal cortex in the cardiovascular responses of the CLa. The effect of microinjection of l-glutamate (50-100 nl, 0.25 M) was tested throughout the Cla and only in one area at 2.7 mm rostral to bregma, 1.8-2.0 midline and 4.5-5.6mm vertical, significant decreases in arterial pressure were elicited (-21.71±2.1 mmHg, P<0.001, t-test) with no significant change in heart rate. Administration (i.v.) of the muscarinic receptor blocker, atropine, had no effect on the change in mean arterial pressure in response to glutamate stimulation, suggesting that the parasympathetic system was not involved in this response. However, administration (i.v.) of the nicotinic receptor blocker, hexamethonium dichloride abolished the depressor response to glutamate, suggesting that CLa stimulation decreases sympathetic outflow to the cardiovascular system. In addition, microinjection of the reversible synaptic blocker, cobalt chloride, into the medial prefrontal cortex greatly attenuated the depressor response elicited by microinjection of glut into the CLa. Thus for the first time, we found the cardiovascular responsive region of the anterior claustrum. Also we showed that its response is mediated through the medial prefrontal cortex.

Hemodynamic responses and serum nitrite concentration during uncontrolled hemorrhagic shock in normotensive and hypertensive rats.

BACKGROUND: We evaluated the effect of hypertension on hemodynamic responses and serum nitrite concentrations in normotensive (NT) and deoxycorticosteron acetate (DOCA)-Salt hypertensive (HT) rats. METHODS: Uncontrolled hemorrhagic shock was induced in NT and HT rats (n=7 each) by preliminary bleed of 25 ml/kg followed by a 75% tail amputation. The mean arterial pressure (MAP), heart rate and serum nitrite were measured pre-hemorrhage and during hemorrhage. RESULTS: Changes in time-averaged MAP after hemorrhage were significantly greater in HT group than NT. After resuscitation, the HT rats failed to restore MAP to baseline level. Serum nitrite level in both groups was significantly increased during shock period. Survival rate of HT animals was lower than NT group, although it was not statistically significant. CONCLUSIONS: Marked reduction of MAP and less improvement after resuscitation suggested the less adaptation of cardiovascular system in HT animals which may interfere with management of these subjects during uncontrolled hemorrhagic shock.

Role of cuneiform nucleus in regulation of sympathetic vasomotor tone in rats.

The cuneiform nucleus (CnF) is a sympathoexcitatory area involved in the central cardiovascular regulation. Its role in the maintaining vasomotor tone has, however, not yet been clarified. In the present study the effects of cobalt chloride (CoCl(2)) a nonselective synapse blocker and NMDA and non-NMDA glutamate receptors on resting mean arterial blood pressure and heart rate of CnF have been evaluated. CoCl(2), AP5 (an NMDA receptor antagonist) and CNQX (an AMPA/kinase receptor antagonist) (100nl) were microinjected into the CnF of anesthetized rats. The blood pressure and heart rate were recorded throughout the experiment. The responses of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of CoCl(2), AP5 and CNQX did not change the basal blood pressure and heart rate. In conclusion, our present study indicates that the CnF is not important in the regulation of cardiovascular tone.

Protective role of selective nitric oxide synthase inhibitor for treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats.

INTRODUCTION: Different vasoactive factors can modulate cardiovascular adaptation to hemorrhagic shock including Nitric Oxide (NO). In this study we investigated the effect of the NO synthase inhibitor for treatment of decompensated hemorrhagic shock in normotensive and hypertensive rats. METHODS: Twenty-four male Wistar rats were divided into two groups: The normotensive and hypertensive groups. Hypertension was induced by the DOCA-Salt method for eight weeks. Then, the animals were given hemorrhagic shock by continuously withdrawing blood until the mean arterial pressure (MAP) reached to 40 mmHg. The animals were maintained in the shock state for 120 minutes. Subsequently, they were randomly assigned to L-NAME-treated and non-treated groups and monitored for 60 minutes. The survival time was recorded. Blood samples were taken before and after the shock and 60 minutes after L-NAME administration. RESULTS: Infusion of L-NAME caused a significant increase in MAP in normotensive animals, however, slightly increased MAP in hypertensive animals. The heart rate did not significantly alter. Hemorrhage caused a marked increase in serum nitrite levels in both groups (P<0.05). L-NAME treatment significantly reduced the serum nitrite concentration in the normotensive group (P<0.05), without any change in the hypertensive group. All animals who received L-NAME treatment survived at the end of experiment. Fifty percent of the hypertensive animals died four hours after the experiment. The 72-hour survival rate was similar in the L-NAME treated groups. CONCLUSION: L-NAME infusion during decompensated hemorrhagic shock plays a protective role in the improvement of hemodynamic responses and short-term survival rate in normotensive animals.

The role of the cholinergic system of the bed nucleus of the stria terminalis on the cardiovascular responses and the baroreflex modulation in rats.

The bed nucleus of the stria terminalis (BST) is a limbic structure involved in cardiovascular regulation and modulation of responses to stress. The BST contains high levels of muscarinic receptors. This study was performed to find the effects of cholinergic system of the BST on the cardiovascular regulation and the baroreflex modulation in rats. Drugs (50-100nl) were microinjected into the BST of 53 urethane anesthetized male rats. The mean arterial pressure and heart rate changes were measured. The baroreflex gain was evaluated by finding the slope of the reflex bradycardia in response to increases in mean arterial pressure due to phenylephrine injection (i.v.). We found that microinjection of acetylcholine (3 and 6nmol/50nl) into the BST increased mean arterial pressure and had no effect on heart rate. Local microinjection of homatropine abolished the effect of Ach on the cardiovascular responses indicating involvement of muscarinic receptors. Local injection of homatropine did not affect the reflexive bradycardia. Local injection of acetylcholine decreased the slope of the reflexive bradycardia indicating that Ach system of the BST inhibits the baroreflex. Acute ablation of the BST by cobalt chloride also significantly decreased the slope, indicating the excitatory action of the BST on the baroreflex parasympathetic component. In conclusion, we showed for the first time that microinjection of acetylcholine into the BST evokes a pressor response by activating the local muscarinic receptors. Release of Ach into the BST, probably during stress, inhibits the baroreflex, but with no stress, the BST facilitates the baroreflex.

Effect of glutamate stimulation of the cuneiform nucleus on cardiovascular regulation in anesthetized rats: role of the pontine Kolliker-Fuse nucleus.

Cuneiform nucleus (CnF) is a reticular nucleus of the midbrain involved in cardiovascular function and stress. There is no report on the cardiovascular effects of the glutamatergic system in the CnF. In the present study, we investigated the cardiovascular effects of glutamate and its NMDA and AMPA/kainate receptors in the CnF. In addition, the possible mediation of Kolliker-Fuse (KF) nucleus in the cardiovascular effects of the CnF was explored. l-glutamate, AP5 (an NMDA receptor antagonist), and CNQX (an AMPA/kainate receptor antagonist) (50-100 nl) were microinjected into the CnF of anesthetized rats. Also, the KF was blocked by cobalt chloride (CoCl(2)) then l-glutamate was microinjected into the CnF. The maximum changes of blood pressure and heart rate were compared with the pre-injection (paired t-test) and control (independent t-test) values. Microinjection of glutamate (25 nmol/100 nl) into the CnF produced either a short pressor and bradycardic or a long pressor and tachycardic responses. Microinjection of AP5 or CNQX alone did not affect the basal arterial pressure and heart rate. However, co-injection of glutamate with AP5 strongly attenuated the short and moderately attenuated the long cardiovascular responses elicited by glutamate. Co-injection of glutamate with CNQX did not attenuate the short and weakly attenuated the long cardiovascular responses elicited by glutamate. These data suggest that the responses are mediated mainly through NMDA receptors. Blockade of the KF nucleus strongly attenuated the short response and weakly attenuated the long response to glutamate microinjection, suggesting that the cardiovascular effects of glutamate in the CnF, especially the short responses, were mediated by the KF nucleus.

Effects of hypertension on hemodynamic response and serum nitrite concentration during graded hemorrhagic shock in rats.

BACKGROUND: Hypertensive patients have higher morbidity and mortality from hemorrhage. In this study, we investigated hemodynamic responses and serum nitrite concentrations during graded hemorrhagic shock and resuscitation in hypertensive (HT) and normotensive (NT) rats. METHODS: Thirteen male rats were divided into two groups, namely HT (n = 6) and NT (n = 7). Hypertension was induced by deoxycorticosterone acetate (DOCA)-salt method in uninephrectomized rats. After 8 weeks, graded hemorrhagic shock was induced during 34 minutes in four steps separated by 8-minute intervals (totally 16 ml/kg). The animals were kept in this condition for 120 minutes (shock period). Then, they were resuscitated with blood withdrawal. Mean arterial pressure (MAP) and heart rate (HR) were measured throughout the experiment. Blood samples were taken before and after shock induction and at the end of the shock period. RESULTS: HT rats experienced more MAP and HR reduction during the shock period and less improvement of hemodynamic response after resuscitation compared with the NT group (p < 0.05). The survival rate 72 hours post-hemorrhage in the HT group was significantly lower than the NT group (16.7% vs. 71.4%, respectively) (p < 0.05). Serum nitrite level in HT animals was lower than the NT group (2.45 ± 0.18 vs. 3.35 ± 0.26 ΅mol/lit, respectively; p < 0.05). In addition, it increased during the shock period in both NT and HT groups (p > 0.05). CONCLUSIONS: More reduction of MAP after hemorrhagic shock, less improvement of MAP and HR after resuscitation and low survival rate in HT animals suggested the impairment of cardiovascular system adaptation of HT animals during blood loss and it should be considered in management of hypertensive subjects.