ascorbic-acid and Bradycardia

Hypertension is associated to an increase in central oxidative stress and an attenuation of the baroreflex control of arterial pressure. The present study evaluated the effect of alterations in the levels of nitric oxide (NO) and superoxide anion in the caudal ventrolateral medulla (CVLM), a key area of the brainstem for the baroreflex control of arterial pressure, in renovascular hypertensive rats (2K1C). Baseline mean arterial pressure (MAP), heart rate (HR), and reflex bradycardia were evaluated 30 days after renal artery occlusion in anesthetized (urethane, 1.2 g/kg, i.p.) 2K1C or normotensive (SHAM) rats. The MAP, HR, and baroreflex control of HR were evaluated before and after CVLM microinjections of the non-selective NOS inhibitor L-NAME (10 nmol), the NO precursor L-ARG (50 nmol), or the antioxidant ascorbic acid, Vit C (10 nmol). In both 2K1C and SHAM animals, CVLM microinjection of L-NAME produced a decrease in MAP, whereas L-ARG induced a significant increase in MAP. However, microinjection of Vit C into the CVLM produced a decrease in MAP and HR only in 2K1C and not in SHAM rats. Cardiovascular effects produced by microinjection of l-ARG into the CVLM were abolished by prior microinjection of L-NAME in the CVLM of 2K1C and SHAM rats. Microinjection of L-NAME into the CVLM increased the sensitivity of reflex bradycardia in 2K1C animals. In contrast, the CVLM microinjection of L-ARG reduced reflex bradycardia only in SHAM rats. Vit C in the CVLM did not change reflex bradycardia in either 2K1C or in SHAM rats. These results suggest that increased oxidative stress in the CVLM during hypertension contributes to the reduced baroreflex sensitivity and to maintain hypertension in the 2K1C model.

Topics: Analysis of Variance; Animals; Arginine; Ascorbic Acid; Baroreflex; Blood Pressure; Bradycardia; Heart Rate; Hypertension, Renovascular; Male; Medulla Oblongata; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase Type I; Nitric Oxide Synthase Type III; Phenylephrine; Rats; Rats, Inbred F344; Regression Analysis; Superoxides

The nucleus tractus solitarius (NTS), a major hindbrain area involved in cardiovascular regulation, receives primary afferent fibers from peripheral baroreceptors and chemoreceptors. Hydrogen peroxide (H(2)O(2)) is a relatively stable and diffusible reactive oxygen species (ROS), which acting centrally, may affect neural mechanisms. In the present study, we investigated effects of H(2)O(2) alone or combined with the glutamatergic antagonist kynurenate into the NTS on mean arterial pressure (MAP) and heart rate (HR). Conscious or anesthetized (urethane and alpha-chloralose) male Holtzman rats (280-320 g) were used. Injections of H(2)O(2) (125 to 1500 pmol/40 nl) into the intermediate NTS of anesthetized rats evoked dose-dependent and transient hypotension (-18 +/- 3 to -55 +/- 11 mmHg) and bradycardia (-16 +/- 5 to -116 +/- 40 bpm). Injection of the catalase inhibitor 3-amino-1,2,4-triazole (100 nmol/40 nl) into the NTS also produced hypotension and bradycardia. Previous injection of the ionotropic L-glutamate receptor antagonist kynurenate (7 nmol/40 nl) attenuated by 48% the bradycardic response, without changing the hypotension evoked by H(2)O(2) (500 pmol/40 nl) in anesthetized rats. The antioxidant L-ascorbate (600 pmol/80 nl) injected into the NTS attenuated the bradycardic (42%) and hypotensive (67%) responses to H(2)O(2) (500 pmol/40 nl) into the NTS. In conscious rats, injection of H(2)O(2) (50 nmol/100 nl) into the NTS also evoked intense bradycardia (-207 +/- 8 bpm) and hypotension (-54 +/- 6 mmHg) that were abolished by prior injection of kynurenate (7 nmol/100 nl). The results show that H(2)O(2) into the NTS induces hypotension and bradycardia probably due to activation of glutamatergic mechanisms.

Topics: Amitrole; Anesthesia; Animals; Ascorbic Acid; Blood Pressure; Bradycardia; Cardiovascular System; Chloralose; Excitatory Amino Acid Antagonists; Glutamic Acid; Heart Rate; Hydrogen Peroxide; Hypotension; Kynurenic Acid; Male; Rats; Rats, Sprague-Dawley; Solitary Nucleus; Urethane

Few studies have examined the effect of acute pressure overload on endothelial function in the coronary microcirculation.. In instrumented conscious dogs with heart rate held constant, veratrine caused a cholinergic nitric oxide (NO)-dependent increase in coronary blood flow by 23+/-3 mL/min (Bezold-Jarisch reflex). Ten minutes after release of constriction of the ascending aorta to increase left ventricular (LV) systolic pressure to 214+/-5 mm Hg for 30 minutes, the veratrine-induced increase in coronary blood flow (7+/-1 mL/min) was reduced by 66% and remained depressed for 2 hours (ie, endothelial stunning [ES]). Nitrite production from isolated coronary microvessels during ES was not different from normal. Ascorbic acid (AA), losartan, or apocynin prevented ES. Myocardial oxygen consumption (MVO2) of LV tissue was measured in vitro in response to bradykinin with preincubation of angiotensin II for 30 minutes. Bradykinin (10(-4) mol/L)-induced reduction in MVO2 was reversed in a concentration-dependent manner by angiotensin II (38+/-1% versus 19+/-2% at 10(-8) mol/L) and restored by coincubation of AA (37+/-2%), tempol (33+/-2%), losartan (34+/-2%), or apocynin (36+/-1%). Exogenous NO-induced reduction in MVO2 was not altered by angiotensin II. Angiotensin II increased lucigenin-detectable superoxide anion in LV tissue in a manner that was inhibited by bradykinin, AA, tempol, losartan, or apocynin.. Endothelial stunning is caused by oxidant processes inhibited by ascorbate, and the activation of NAD(P)H oxidase by increased angiotensin II plays an important role in this process.

Topics: Acetophenones; Angiotensin II; Animals; Ascorbic Acid; Bradycardia; Bradykinin; Coronary Circulation; Cyclic N-Oxides; Dogs; Hypotension; Ligation; Losartan; Myocardial Stunning; Nitric Oxide; Oxidative Stress; Pressure; Reflex; Spin Labels; Superoxides; Veratrine

The antioxidants, Trolox (6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid, a water soluble analog of vitamin E) and ascorbic acid (AA), protect the heart from ischemia-reperfusion injury. We hypothesized that maternal infusion of Trolox and AA, would reduce the fetal bradycardia and myocardial damage observed in fetal hypoxia and increase the total antioxidant activity in fetal plasma. Either i.v. saline (control group) or Trolox + AA (drug group) was randomly administered to 29-d-old pregnant rabbits. Fetal hypoxia was induced by uterine ischemia. Fetal heart rate, plasma CK-MB activity, and plasma total radical antioxidant potential (TRAP) were measured in different sets of animals. Fetal heart rate in the drug group was higher than in the control group for the first 35 min (p < 0.05 at every 5-min interval). Fetal bradycardia (<60 beats/min) occurred after 39 min (median) in the drug group, and 29 min in the control group (p < 0.05). After 50 min of hypoxia, plasma CK-MB was lower in the drug group, 1204 +/- 132 U/L (mean +/- SEM), than in the control group, 2633 +/- 233 U/L (p < 0.05). TRAP was higher in the drug group, 3.01 +/- 0.15 mM (Trolox equivalent concentration), than in the control group, 1.48 +/- 0.27 mM (p < 0.05). Higher TRAP levels (> or = 2.0 mM) were associated with lower CK-MB levels (<2500 U/L) (p < 0.05). Administration of Trolox and AA to the mother has a beneficial effect on fetal myocardial damage after fetal hypoxia, and a small beneficial effect on fetal bradycardia during hypoxia. The beneficial effect may be due to the augmentation of fetal plasma antioxidants from maternal antioxidant pretreatment.

Topics: Animals; Antioxidants; Ascorbic Acid; Bradycardia; Chromans; Creatine Kinase; Female; Fetal Hypoxia; Heart; Pregnancy; Rabbits; Reperfusion Injury; Survival