Commissural nucleus of the solitary tract regulates the antihypertensive effects elicited by moxonidine.

The rostral ventrolateral medulla (RVLM) contains the presympathetic neurons involved in cardiovascular regulation that has been implicated as one of the most important central sites for the antihypertensive action of moxonidine (an α2-adrenergic and imidazoline agonist). Here, we sought to evaluate the cardiovascular effects produced by moxonidine injected into another important brainstem site, the commissural nucleus of the solitary tract (commNTS). Mean arterial pressure (MAP), heart rate (HR), splanchnic sympathetic nerve activity (sSNA) and activity of putative sympathoexcitatory vasomotor neurons of the RVLM were recorded in conscious or urethane-anesthetized, and artificial ventilated male Wistar rats. In conscious or anesthetized rats, moxonidine (2.5 and 5 nmol/50 nl) injected into the commNTS reduced MAP, HR and sSNA. The injection of moxonidine into the commNTS also elicited a reduction of 28% in the activity of sympathoexcitatory vasomotor neurons of the RVLM. To further assess the notion that moxonidine could act in another brainstem area to elicit the antihypertensive effects, a group with electrolytic lesions of the commNTS or sham and with stainless steel guide-cannulas implanted into the 4th V were used. In the sham group, moxonidine (20 nmol/1 µl) injected into 4th V decreased MAP and HR. The hypotension but not the bradycardia produced by moxonidine into the 4th V was reduced in acute (1 day) commNTS-lesioned rats. These data suggest that moxonidine can certainly act in other brainstem regions, such as commNTS to produce its beneficial therapeutic effects, such as hypotension and reduction in sympathetic nerve activity.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke.

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 µg/kg, bolus) and a depressor dose of sodium nitroprusside (50 µg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 µL) into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

Effects of the administration of a catalase inhibitor into the fourth cerebral ventricle on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats. .

Sidestream cigarette smoke effects on cardiovascular responses in conscious rats: involvement of oxidative stress in the fourth cerebral ventricle.

BACKGROUND: Cigarette exposure increases brain oxidative stress. The literature showed that increased brain oxidative stress affects cardiovascular regulation. However, no previous study investigated the involvement of brain oxidative stress in animals exposed to cigarette and its relationship with cardiovascular regulation. We aimed to evaluate the effects of central catalase inhibition on baroreflex and cardiovascular responses in rats exposed to sidestream cigarette smoke (SSCS). METHODS: We evaluated males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). Femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. Rats were exposed to SSCS during three weeks, 180 minutes, 5 days/week (CO: 100-300 ppm). Baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 µg/kg, bolus) to induce bradycardic reflex and a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, bolus) to induce tachycardic reflex. Cardiovascular responses were evaluated before, 5, 15, 30 and 60 minutes after 3-amino-1,2,4-triazole (ATZ, catalase inhibitor, 0.001 g/100 µL) injection into the 4th V. RESULTS: Central catalase inhibition increased basal HR in the control group during the first 5 minutes. SSCS exposure increased basal HR and attenuated bradycardic peak during the first 15 minutes. CONCLUSION: We suggest that SSCS exposure affects cardiovascular regulation through its influence on catalase activity.

Catalase inhibition into the fourth cerebral ventricle affects bradycardic parasympathetic response to increase in arterial pressure without changing the baroreflex.

Exogenous catalase influences neural control of cardiovascular system; however, we do not know yet if its inhibition into the fourth cerebral ventricle (4(th) V) influences baroreflex regulation. We evaluated the effects of central catalase inhibition on baroreflex in conscious Wistar rats. We used males Wistar rats (320-370 g), which were implanted with a stainless steel guide cannula into 4(th) V. The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. After basal MAP and HR recordings, the baroreflex was tested with a pressor dose of phenylephrine (PHE, 8 µg/kg, bolus) and a depressor dose of sodium nitroprusside (SNP, 50 µg/kg, bolus). Baroreflex was evaluated before 5, 15, 30 and 60 minutes after 3-amino-1, 2, 4-triazole (ATZ, 0.001 g/100 µL) injection into the 4(th) V. Vehicle treatment did not change baroreflex responses. ATZ attenuated bradycardic peak and reduced HR range at 30 minutes. ATZ into the 4(th) V reduced bradycardic and tachycardic reflex responses to increase and decrease MAP, respectively (p<0.05) 30 minutes after its microinjection without significantly changing the basal MAP and HR. In conclusion, central catalase inhibition influenced the highest parasympathetic response to MAP increase in conscious Wistar rats without change baroreflex gain.

The effects of catalase inhibition into the fourth cerebral ventricle on the Bezold-Jarisch reflex in spontaneously hypertensive rats.

Many studies have investigated the role of oxidative stress on cardiovascular system in the brainstem of spontaneously hypertensive rats (SHR). However, we do not know yet if catalase inhibition influences cardiopulmonary reflex (Bezol-Jarisch reflex). Thus, we aimed to evaluate the effects of central catalase inhibition on cardiopulmonary reflex in SHR. Males Wistar Kyoto (WKY) rats and SHR were implanted with a stainless steel guide cannula into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for mean arterial pressure (MAP) and heart rate (HR) measurement and drug infusion, respectively. The cardiopulmonary reflex was tested with phenylbiguanide (PBG, 8 µg/kg, bolus, i.v.). Cardiopulmonary reflex was evaluated before and 15 minutes after 3-amino-1,2,4-triazole (ATZ, 0.01 g/100 µL) injection into the 4th V. Vehicle treatment did not change basal MAP and HR and cardiopulmonary reflex responses in SHR and WKY rats. Central ATZ increased hypotensive (p=0.038) responses without influencing the bradycardic reflex (p=0.287) in WKY rats. In SHR, ATZ increased hypotension (p=0.0004) and bradycardic (p=0.04) responses to i.v. PBG. No changes were observed regarding basal MAP and HR after ATZ injection in SHR and WKY rats. We suggest central catalase inhibition affects cardiopulmonary reflex with more intensity in SHR compared to WKY rats.

ATZ (3-amino-1,2,4-triazole) injected into the fourth cerebral ventricle influences the Bezold-Jarisch reflex in conscious rats.

OBJECTIVES: Many studies have investigated the importance of oxidative stress on the cardiovascular system. In this study we evaluated the effects of central catalase inhibition on cardiopulmonary reflex in conscious Wistar rats. METHODS: Male Wistar rats were implanted with a stainless steel guide cannula in the fourth cerebral ventricle. The femoral artery and vein were cannulated for mean arterial pressure and heart rate measurement and for drug infusion, respectively. After basal mean arterial pressure and heart rate recordings, the cardiopulmonary reflex was tested with a dose of phenylbiguanide (PBG, 8 µg/kg, bolus). Cardiopulmonary reflex was evaluated before and µ l15 minutes after 1.0 µl 3-amino-1,2,4-triazole (ATZ, 0.01 g/100 µl)0.01 g/100 µl) injection into the fourth cerebral ventricle. Vehicle treatment did not change cardiopulmonary reflex responses. RESULTS: Central ATZ significantly increased hypotensive responses without influencing the bradycardic reflex. CONCLUSION: ATZ injected into the fourth cerebral ventricle increases sympathetic inhibition but does not change the parasympathetic component of the cardiopulmonary reflex in conscious Wistar rats.

ATZ (3-amino-1,2,4-triazole) injected into the fourth cerebral ventricle influences the Bezold-Jarisch reflex in conscious rats

OBJECTIVES: Many studies have investigated the importance of oxidative stress on the cardiovascular system. In this study we evaluated the effects of central catalase inhibition on cardiopulmonary reflex in conscious Wistar rats. METHODS: Male Wistar rats were implanted with a stainless steel guide cannula in the fourth cerebral ventricle. The femoral artery and vein were cannulated for mean arterial pressure and heart rate measurement and for drug infusion, respectively. After basal mean arterial pressure and heart rate recordings, the cardiopulmonary reflex was tested with a dose of phenylbiguanide (PBG, 8 μg/kg, bolus). Cardiopulmonary reflex was evaluated before and μl15 minutes after 1.0 μl 3-amino-1,2,4-triazole (ATZ, 0.01g/100μl)0.01 g/100 μl) injection into the fourth cerebral ventricle. Vehicle treatment did not change cardiopulmonary reflex responses. RESULTS: Central ATZ significantly increased hypotensive responses without influencing the bradycardic reflex. CONCLUSION: ATZ injected into the fourth cerebral ventricle increases sympathetic inhibition but does not change the parasympathetic component of the cardiopulmonary reflex in conscious Wistar rats.

Central blockade of nitric oxide synthesis reduces moxonidine-induced hypotension.

1. Nitric oxide (NO) and alpha(2)-adrenoceptor and imidazoline agonists such as moxonidine may act centrally to inhibit sympathetic activity and decrease arterial pressure. 2. In the present study, we investigated the effects of pretreatment with l-NAME (NO synthesis inhibitor), injected into the 4th ventricle (4th V) or intravenously (i.v.), on the hypotension, bradycardia and vasodilatation induced by moxonidine injected into the 4th V in normotensive rats. 3. Male Wistar rats with a stainless steel cannula implanted into the 4th V and anaesthetized with urethane were used. Blood flows were recorded by use of miniature pulsed Doppler flow probes implanted around the renal, superior mesenteric and low abdominal aorta. 4. Moxonidine (20 nmol), injected into the 4th V, reduced the mean arterial pressure (-42+/-3 mmHg), heart rate (-22+/-7 bpm) and renal (-62+/-15%), mesenteric (-41+/-8%) and hindquarter (-50+/-8%) vascular resistances. 5. Pretreatment with l-NAME (10 nmol into the 4th V) almost abolished central moxonidine-induced hypotension (-10+/-3 mmHg) and renal (-10+/-4%), mesenteric (-11+/-4%) and hindquarter (-13+/-6%) vascular resistance reduction, but did not affect the bradycardia (-18+/-8 bpm). 6. The results indicate that central NO mechanisms are involved in the vasodilatation and hypotension, but not in the bradycardia, induced by central moxonidine in normotensive rats.

Systemic site of action for pressor effect of angiotensin II injected into the fourth cerebral ventricle of rats?

Angiotensin II (ANG II) causes a systemic pressor effect when injected into the cerebral ventricles. In the rat fourth ventricle, the effective doses for the ANG II pressor effect are over 100 times larger than in the systemic circulation. Considering the discrepancy of doses, the possibility that ANG II may reach the systemic circulation and promote pressor effects, following injection into the fourth ventricle, was investigated. The effects on blood pressure of different vasoactive peptides that produce pressor responses when injected into the central nervous system were compared. Dose-response curves were obtained for intravenous or fourth cerebroventricular injections of ANG II, lysyl-vasopressin (LVP), bradykinin (BK), or endothelin-1 (ET-1). The ED50 ratios for intracerebroventricular/intraveneous injections were 110 for ANG II, 109 for LVP, 0.01 for BK, and approximately 0.4 for ET-1. In cross-circulation preparations, pressor responses occurred in the donor rat following injection into the fourth cerebral ventricle of the recipient animal, showing that effective doses of ANG II, administered to the fourth cerebral, reach the systemic circulation. The same results were obtained for the microinjection of 4 nmol of LVP into the fourth cerebral ventricle of recipient animals. High-performance reverse-phase liquid chromatography analyses of arterial blood showed that approximately 1% of the [125I]ANG II injected into the fourth cerebral ventricle may be recovered from the systemic circulation a few seconds after the microinjection. The systemic administration of the ANG II receptor antagonist losartan blocked the response to ANG II injected into the fourth ventricle whereas antagonist administration in the same ventricle did not. Angiotensin injections into the lateral ventricle produced pressor responses that were reduced by antagonist administration to the same ventricle but not by systemic administration of the antagonist. The data suggest that the pressor effect resulting from ANG II or LVP injections into the fourth cerebral ventricle may be due to the action of this peptide in the systemic circulation. On the other hand, the pressor effect due to ANG II microinjection into the lateral ventricle apparently results from the direct stimulation of central periventricular structures.