veratrine and Hypotension

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

With cats anaesthetized with sodium pentobarbital we studied how veratrine-induced reflexes interact with cough. Cough was elicited by mechanical stimulation of tracheobronchial mucosa and its intensity was evaluated from the changes in oesophageal pressure. Veratrine injected intravenously produced apnoea, bradycardia and long-lasting hypotension. With each dose the intensity of cough was significantly decreased during the apnoea. When the mechanical stimulus was repeated during the breathing following apnoea with remaining hypotension, cough intensity parameters were not changed from control. Veratrine injected intracardially caused bradycardia, hypotension, and decreases in respiratory rate and tidal volume. The intensity of cough elicited just after injection of veratrine was also significantly decreased. We suggest that veratrine-induced reflexes depress the cough reflex mainly by inhibitory reflexes arising from cardiac receptors. The inhibition of cough is probably mediated indirectly via the inhibition of medullary respiratory neurons.

Topics: Animals; Apnea; Bradycardia; Cats; Cough; Dose-Response Relationship, Drug; Female; Heart; Hypotension; Injections, Intravenous; Male; Reflex; Veratrine

The present study was undertaken to determine whether intracoronary (left circumflex) veratrine (ICV) infusions and increases in left ventricular (LV) systolic pressure influence renal circulatory and excretory function in chronically instrumented conscious dogs (n = 19). Thirty minutes of ICV infusions decreased arterial pressure by 15-20 mmHg, but heart rate, urine flow, sodium excretion, and free water clearance did not change. Intravenous nitroprusside infusions, which also lowered arterial pressure by 15-20 mmHg, increased heart rate while urine flow, sodium excretion, and free water clearance were significantly decreased. Heart rate and renal excretory function also did not change during a 15- to 20-mmHg decrease in arterial pressure when LV systolic pressure was simultaneously raised to approximately 170 mmHg by ascending aortic occlusion. The topical application of a local anesthetic in the region of the left main coronary artery abolished the Bezold-Jarisch reflex and the attenuation of hypotension-induced salt and water retention and tachycardia by ICV. Renal plasma flow and glomerular filtration rate were not altered during any of the above experimental treatments. These results suggest that in the conscious dog chemical and mechanical stimulation of LV sensory receptors with afferents in the pericoronary region can modulate the neurohumoral reflex control of renal excretory function independent of local filtration effects.

Topics: Animals; Aortic Valve Stenosis; Blood Pressure; Cardiac Catheterization; Consciousness; Dogs; Heart Rate; Hypotension; Kidney; Male; Nitroprusside; Renal Circulation; Time Factors; Urination; Veratrine

Cardiovascular responses to intravenous bolus doses of certain exogenous substances (capsaicin, phenyldiguanide, cryptenamine, veratrine sulphate) which act on chemoreceptors in the pulmonary or proximal arterial circulation were compared to the naturally occurring chemoreceptor agonist, leucineenkephalin (Leu5-ENK) in the conscious dog. Capsaicin (40 micrograms/kg) and phenyldiguanide (40 micrograms/kg) produced hypotension and bradycardia 5 to 12 sec after injection (P less than 0.05) followed by hypertension (P less than 0.05). Cryptenamine (5 micrograms/kg) produced only hypotension and bradycardia (P less than 0.05) whereas Leu5-ENK (35 micrograms/kg) produced only hypertension and tachycardia (P less than 0.05). The hypotension and bradycardia produced by capsaicin and phenyldiguanide occurred earlier than the pressor response to Leu5-ENK, capsaicin, and phenyldiguanide and the depressor response to veratrine (P less than 0.05). Cryptenamine (5 micrograms/kg) and Leu5-ENK (35 micrograms/kg) when given together had additive effects on heart rate but interacted significantly in influencing blood pressure (P less than 0.05). It is concluded that the early response to capsaicin and phenyldiguanide are compatible with stimulation of known pulmonary chemoreceptors (including J receptors) whereas the pressor effect of phenyldiguanide and Leu5-ENK and the depressor response to veratrum alkaloids are due to activation of receptors in the proximal arterial circulation. The influence of Leu5-ENK on the haemodynamic response to veratrine suggest that ENK may modulate the Bezold-Jarisch reflex.

Topics: Animals; Biguanides; Blood Pressure; Bradycardia; Capsaicin; Cardiovascular System; Chemoreceptor Cells; Dogs; Drug Combinations; Drug Interactions; Enkephalin, Leucine; Female; Heart Rate; Hypotension; Injections, Intravenous; Male; Protoveratrines; Veratrine

The Bezold-Jarisch-like effect (BJE) induced by 2.5 micrograms/100 g of veratridine injected intravenously or into the left ventricle was studied in anesthetized rats. The possible potentiation of the effect by a small dose (10 micrograms/100 g) of a purified scorpion toxin (tityustoxin) was also investigated. Heart rate (HR), electrocardiogram (ECG), mean arterial pressure (MAP) and respiratory rate (RR) were recorded. Intravenous (iv) injection of veratridine induced a BJE consisting of slight bradycardia in 4 out of 8 experiments, fall of MAP (from 107 +/- 3 to 90 +/- 4 mmHg) and apnea. The control RR was 105 +/- 5 insp/min and apnea, after veratridine, lasted 8 +/- 2 s. The BJE evoked by injection of a second dose of veratridine was potentiated 20 min after an iv injection of tityustoxin. The HR decreased from 334 +/- 16 to 108 +/- 17 beats/min, the MAP fell from 110 +/- 5 to 68 +/- 4 mmHg and the control RR of 92 +/- 5 insp/min was followed by a long period of apnea (68 +/- 17 s). Injection of veratridine into the left ventricle (lv) evoked a BJE characterized by slight bradycardia in 5 out of 10 experiments, arterial hypotension (from 110 +/- 6 to 89 +/- 6 mmHg) and tachypnea (from 82 +/- 6 to 102 +/- 7 insp/min). The effects induced by a second dose of veratridine were potentiated 20 min after an lv injection of tityustoxin. The HR decreased from 377 +/- 14 to 119 +/- 18 beats/min, the MAP fell from 119 +/- 5 to 72 +/- 10 mmHg and the RR increased from 80 +/- 6 to 117 +/- 9 insp/min. This tachypnea was followed by bradypnea 20 s later (21 +/- 6 insp/min). The ECG showed that hypotension induced by iv or lv injections of veratridine coincided with a slight sinus bradycardia before tityustoxin (N = 9) and A-V block after the toxin (N = 18). Cervical bilateral vagotomy prevented the cardiac and respiratory effects induced by lv veratridine in tityustoxin-treated rats, but a slight hypotension was still recorded (from 114 +/- 10 to 94 +/- 10 mmHg, P less than 0.05). Injection of veratridine (2.5 micrograms/100 g) into the ascendent aorta evoked a slight hypotension (from 105 +/- 6 to 87 +/- 7 mmHg, P less than 0.05) and tachypnea followed by bradypnea, but bradycardia was not recorded.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Animals; Apnea; Blood Pressure; Bradycardia; Drug Synergism; Electrocardiography; Heart Rate; Heart Ventricles; Hypotension; Injections; Injections, Intra-Arterial; Injections, Intravenous; Male; Rats; Reflex; Respiration; Scorpion Venoms; Vagotomy; Veratridine; Veratrine

Topics: Acetylcholine; Biomechanical Phenomena; Bradycardia; Chloroform; Chlorpromazine; Depression, Chemical; Electric Stimulation; Ethers; Halothane; Heart; Hypotension; Kinetics; Models, Biological; Muscle Contraction; Myocardium; Plants, Medicinal; Plants, Toxic; Vagus Nerve; Veratrine; Veratrum