aconitine and Hypertension

Within urban air sheds, specific ambient air pollutants typically peak at predictable times throughout the day. For example, in environments dominated by mobile sources, peak nitrogen dioxide (NO2) levels coincide with morning and afternoon rush hours, while peak levels of ozone (O3), occur in the afternoon.. Given that exposure to a single pollutant might sensitize the cardiopulmonary system to the effects of a subsequent exposure to a second pollutant, we hypothesized that a morning exposure to NO2 will exaggerate the cardiovascular effects of an afternoon O3 exposure in rats.. Rats were divided into four groups that were each exposed for 3 h in the morning (m) and 3 h in the afternoon (a) on the same day: (1) m-Air/a-Air, (2) m-Air/a-O3 (0.3 ppm), (3) m-NO2 (0.5 ppm)/a-Air and (4) m-NO2/a-O3. Implanted telemetry devices recorded blood pressure and electrocardiographic data. Sensitivity to the arrhythmogenic agent aconitine was measured in a separate cohort.. Only m-NO2/a-O3-exposed rats had significant changes in electrophysiological, mechanical and autonomic parameters. These included decreased heart rate and increased PR and QTc intervals and increased heart rate variability, suggesting increased parasympathetic tone. In addition, only m-NO2/a-O3 exposure decreased systolic and diastolic blood pressures and increased pulse pressure and QA interval, suggesting decreased cardiac contractility.. The findings indicate that initial exposure to NO2 sensitized rats to the cardiovascular effects of O3 and may provide insight into the epidemiological data linking adverse cardiovascular outcomes with exposures to low concentrations of O3.

Topics: Aconitine; Administration, Inhalation; Air Pollutants; Animals; Arrhythmias, Cardiac; Blood Pressure; Electrocardiography; Heart Rate; Hypertension; Male; Nitrogen Dioxide; Ozone; Rats; Rats, Inbred SHR

The present work was designed to investigate the relationship between hemodynamic parameters and the susceptibility of ventricular arrhythmia to aconitine in conscious Lyon hypertensive rats (LH).. Male LH and Lyon low blood pressure rats (LL) were used. After the determination of baroreflex sensitivity (BRS), ventricular arrhythmia was induced by aconitine infusion in conscious rats. Blood pressure (BP) was recorded during the period of infusion.. Compared with the LL rats, the LH rats possessed significantly higher BP, blood pressure variability and lower BRS. The threshold of aconitine required for ventricular fibrillation and cardiac arrest in the LH rats were significantly lower than those in the LL rats. It was found that all the hemodynamic parameters studied were not correlated with the threshold of aconitine required for arrhythmia, with the exception of BRS, which was positively related to the threshold of aconitine required for ventricular premature beat.. The LH rats possessed greater susceptibility to aconitine-induced ventricular arrhythmias when compared to the LL rats. This greater susceptibility could not be attributed to any one of the hemodynamic parameters alone studied in the LH rats. It is proposed that various hypertension-associated abnormalities, including the abnormal hemodynamics, may co-contribute to this vulnerability to ventricular arrhythmias.

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Baroreflex; Blood Pressure; Disease Susceptibility; Hypertension; Male; Rats

The present study was designed to test a hypothesis that nonfatal ventricular arrhythmia such as ventricular premature beats (VPB) is a contributing factor in the elevation of blood pressure variability (BPV).. Blood pressure (BP) and electrocardiogram were continuously recorded. The relation between VPB and BPV was observed under conscious state in chronic myocardial infarction (MI) rats one month after ligation of the left coronary artery, and further verified under anesthetized state in rat model of ventricular arrhythmia produced by acute intravenous infusion of aconitine.. MI rats exhibited a big difference in the count and pattern of VPB, and were divided into no VPB, occasional VPB, and frequent VPB groups. Among the three groups, there were no differences in BP, heart period (HP), and MI size. However, BPV was markedly higher in frequent not occasional VPB rats, and HP variability (HPV) was larger in both frequent and occasional VPB rats, when compared with no VPB rats. In the whole population of MI rats, BPV was positively correlated with VPB and HPV, not with BP, HP and MI size. Infusion of aconitine had no effect on BP, HP, BPV, and HPV during the period without VPB. Frequent VPB after several minutes of aconitine infusion induced significant increase in BPV and HPV with no change in BP and HP. BPV was also positively correlated with VPB and HPV, not with BP and HP. Hemodynamics in aconitine-evoked ventricular tachycardia was characterized as lower BP, higher BPV, and higher HPV.. High BPV can be caused by frequent not occasional VPB in rats.

Topics: Aconitine; Animals; Blood Pressure; Heart Rate; Hypertension; Male; Myocardial Infarction; Myocardium; Rats; Rats, Sprague-Dawley; Tachycardia, Ventricular; Ventricular Premature Complexes

Antiarrhythmic activity of oral allapinin was studied in 64 patients with ischemic heart disease. 27 of the patients had undergone coronary artery bypass grafting 2 to 12 months before, 19 patients had postinfarction cardiosclerosis, 38--arterial hypertension, 30--circulation insufficiency stage I. Arrhythmia presented as ventricular extrasystole (n = 28), paroxysmal atrial fibrillation (n = 18), paroxysmal atrial tachycardia (n = 11), frequent supraventricular extrasystole (n = 7). Arrhythmia continued from 6 months to 8 years. An effective single dose was defined with acute pharmacological test. The treatment course lasted for 21 days. Allapinin proved to be highly effective: ventricular ectopic activity was suppressed in 71.4% patients, atrial tachycardia paroxysms were prevented in 72.7%, paroxysms of atrial fibrillation--in 77.8%. Allapinin tolerance was good. Extracardiac side effects occurred most frequently, but dose lowering was necessary only in 6.2%. The drug was discontinued because of cardiac side effects in 4.7% cases. ECG monitoring is a highly informative method of the treatment efficacy control.

Topics: Aconitine; Aged; Anti-Arrhythmia Agents; Arrhythmias, Cardiac; Coronary Artery Bypass; Drug Tolerance; Electrocardiography; Humans; Hypertension; Male; Middle Aged; Monitoring, Physiologic; Myocardial Ischemia; Time Factors

Abnormal central cholinergic activity has been reported to be responsible in part for the pathogenesis of high blood pressure in spontaneously hypertensive rats (SHR). Administration of cholinergic agonists in brain and spinal cord results in exaggerated pressor responses in SHR. Studies to date have focused largely on the muscarinic cholinergic system. Recently, we demonstrated that intrathecal administration of nicotinic agonists results in pressor, tachycardic, and irritation responses. In the present study we examine the cardiovascular and behavioral responses to nicotine and cytisine administered intrathecally in La Jolla strain (LJ) SHRLJ and age-matched Wistar-Kyoto (WKYLJ) rats. Nicotinic agonists produced augmented pressor, heart rate, and irritation responses in SHRLJ compared with normotensive rats. In both SHRLJ and WKYLJ rats, cytisine elicited a greater nociceptive response and greater spinobulbar component to the pressor response than nicotine. SHRLJ and WKYLJ rats also differ in that the SHRLJ strain shows a diminished tendency for desensitization to cytisine. As in Sprague-Dawley rats, in SHRLJ and WKYLJ rats the cardiovascular and behavioral responses to intrathecal nicotine were significantly inhibited by mecamylamine, dihydro-beta-erthyroidine, and methyllycaconitine. However, methyllycaconitine, which effectively blocked cytisine-elicited cardiovascular and behavioral responses in Sprague-Dawley and WKYLJ rats, was unable to inhibit the maximal rise in cystine-elicited blood pressure, heart rate, and irritation responses in SHRLJ. In contrast to the heightened cardiovascular and behavioral responses, the number of nicotinic binding sites in spinal cord membranes was significantly decreased in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Aconitine; Alkaloids; Animals; Azocines; Blood Pressure; Dihydro-beta-Erythroidine; Dose-Response Relationship, Drug; Heart Rate; Hypertension; Injections, Spinal; Male; Mecamylamine; Motor Activity; Nicotine; Nicotinic Agonists; Quinolizines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Spinal Cord; Stereotyped Behavior

To investigate whether the high mortality rate that occurs in streptozotocin (STZ)-diabetic spontaneously hypertensive rats (SHR) is related to abnormalities in glycemic control, in hemodynamics and cardiac function, or in susceptibility to the occurrence of ventricular arrhythmias.. Diabetes was induced in SHR and Wistar-Kyoto (WKY) rats by the intravenous injection of STZ 55 mg/kg. Intraperitoneal glucose tolerance tests were performed after six and 11 weeks. Blood pressure was measured in conscious rats at weeks 0 and 11 with a tail-cuff method and in anesthetized animals at week 12 through a cannulated artery. Response of myocardial function to rapid intravenous infusion of saline 10 mL/kg/min and the times of onset of ventricular arrhythmias during intravenous infusion of aconitine 20 micrograms/kg/min were determined in anesthetized rats at week 12. Plasma samples from the rats were assayed for glucose, insulin, triglycerides and carnitine.. STZ injection caused hyperglycemia, hypoinsulinemia and glucose intolerance equally in SHR and WKY. Diabetic SHR exhibited significant hypertriglyceridemia, depletion in plasma carnitine, impaired responses of blood pressure and myocardial function to rapid intravenous infusion of saline and a 37.5% mortality rate, whereas diabetic WKY did not exhibit these changes. SHR and WKY, diabetic or nondiabetic, were equally sensitive to the induction of ventricular arrhythmias by aconitine infusion.. Mortality of the STZ-diabetic SHR is not due to an exaggeration of the impaired glycemic control, but may be attributed to the occurrence of cardiac dysfunction. The development of life-threatening cardiac arrhythmias, while unlikely, cannot be completely excluded.

Topics: Aconitine; Animals; Arrhythmias, Cardiac; Blood Glucose; Blood Pressure; Carnitine; Diabetes Mellitus, Experimental; Drug Evaluation, Preclinical; Hypertension; Insulin; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Saline Solution, Hypertonic; Streptozocin; Triglycerides