Hypotension In Conscious Dogs Research Articles

Investigation of orthostatic hypotension in conscious dogs within the context of regulatory toxicology studies

Investigation of orthostatic hypotension in conscious dogs within the context of regulatory toxicology studies

Arterial baroreceptors control plasma vasopressin responses to graded hypotension in conscious dogs.

We studied the role of cardiac and arterial baroreceptors in the reflex control of arginine vasopressin (AVP) and renin secretion during graded hypotension in conscious dogs. The dogs were prepared with Silastic cuffs on the thoracic inferior vena cava and catheters in the pericardial space. Each experiment consisted of a control period followed by four periods of inferior vena caval constriction, during which mean arterial pressure (MAP) was reduced in increments of approximately 10 mmHg. The hormonal responses were measured in five dogs under four treatment conditions: 1) intact, 2) acute cardiac denervation (CD) by intrapericardial infusion of procaine, 3) after sinoaortic denervation (SAD), and 4) during combined SAD+CD. The individual slopes relating MAP to plasma AVP and plasma renin activity (PRA) were used to compare the treatment effects using a 2 x 2 factorial analysis. There was a significant (P < 0.01) effect of SAD on the slope relating plasma AVP to MAP but no effect of CD and no SAD x CD interaction. In contrast, the slope relating PRA and MAP was increased (P < 0.05) by SAD but was not affected by CD. These results support the hypothesis that stimulation of AVP secretion in response to graded hypotension is primarily driven by unloading arterial baroreceptors in the dog.

Neurohumoral regulation of the pulmonary circulation during circulatory hypotension in conscious dogs.

We investigated the effects of circulatory hypotension (HYPO) on the left pulmonary vascular pressure-flow relationship in chronically instrumented conscious dogs and the role of five neurohumoral mechanisms in either mediating or modulating the response to this stimulus. HYPO was induced by acute (approximately 15-min) inflation of a hydraulic occluder implanted around the thoracic inferior vena cava, which decreased systemic arterial pressure to approximately 55 mmHg. HYPO resulted in active pulmonary vasoconstriction (53-66%; P < 0.01) in intact conscious dogs. Sympathetic alpha 1-adrenoreceptor block reduced (P < 0.01) the magnitude of HYPO-induced pulmonary vasoconstriction by 91-99%. Neither sympathetic beta-adrenoreceptor block nor cholinergic muscarinic receptor block had any significant effect on the magnitude of HYPO-induced pulmonary vasoconstriction. Surprisingly, angiotensin II receptor block increased (P < 0.05) HYPO-induced pulmonary vasoconstriction by 69-91%. In contrast, arginine vasopressin V1-receptor block reduced (P < 0.05) HYPO-induced pulmonary vasoconstriction by 34-41%. These results indicate that the pulmonary circulation of intact conscious dogs is actively regulated by three distinct neurohumoral mechanisms during HYPO. Sympathetic alpha 1-adrenoreceptor activation is the primary mediator of HYPO-induced pulmonary vasoconstriction. Angiotensin II and arginine vasopressin exert opposing pulmonary vasodilator and vasoconstrictor effects during HYPO, whereas sympathetic beta-adrenoreceptor and cholinergic muscarinic receptor activation do not appear to modulate the pulmonary vascular response to HYPO.

Intracoronary veratrine and acute aortic stenosis modify renal responses to hypotension in conscious dogs

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.

Cortisol inhibition of vasopressin and ACTH responses to arterial hypotension in conscious dogs

We evaluated the role of cortisol as a feedback inhibitor of the vasopressin response to arterial hypotension. Conscious dogs (n = 5) were each studied on 10 different days. There were five different pretreatments: 1) isotonic saline (control), 2) 5.5 or 3) 11 nmol cortisol.kg-1.min-1 iv for 30 min, 4) 6.8 pmol ACTH-(1-24).kg-1.min-1 iv for 30 min, or 5) 1.5 mg dexamethasone im given the night before experimentation. These pretreatments were followed by a stimulus period (30 min) during which mean arterial pressure was decreased a moderate (-19 +/- 1 mmHg) or severe (-29 +/- 1 mmHg) degree with a controlled infusion of intravenous sodium nitroprusside. The vasopressin response to moderate hypotension was not consistently inhibited by any of the pretreatments. In contrast, the large vasopressin response to severe hypotension in the control experiments (from 3.1 +/- 0.3 to 270 +/- 113 pg/ml) was significantly attenuated by cortisol infusion in a dose-dependent manner. Adrenocorticotropin infusion was more effective than dexamethasone as an inhibitor of the vasopressin response to severe hypotension. The data suggest that physiological increases in cortisol inhibit the large increase in vasopressin in response to severe arterial hypotension.

Vasopressin and ANG II in the control of ACTH secretion and arterial and atrial pressures

Hypotension stimulates the secretion of adrenocorticotropin (ACTH) and vasopressin (AVP) and increases plasma levels of angiotensin II (ANG II). Because AVP and ANG II increase ACTH secretion, the present experiments were performed to evaluate the role of these peptides in the increases in plasma ACTH and glucocorticoid concentrations produced by hypotension in conscious dogs. This was accomplished by determining whether administration of receptor antagonists to vasopressin, [1-(beta-mercapto-beta,beta-cyclopentamethylene propionic acid), 2-(O-methyl)tyrosine]Arg8-vasopressin, and ANG II (saralasin), reduced the ACTH and glucocorticoid responses to infusion of four doses of the vasodilator nitroprusside. Nitroprusside (NP) infusion produced dose-dependent decreases in mean arterial pressure. Larger decreases in arterial pressure were produced in dogs pretreated with the AVP antagonist or with both saralasin and the vasopressin antagonist. Left and right atrial pressures also fell with NP infusion, and larger decreases in atrial pressures were found in dogs pretreated with the AVP antagonist. Finally, NP infusion increased plasma glucocorticoid concentration and plasma ACTH concentration. Both the glucocorticoid and the ACTH responses to hypotension were reduced in dogs given the AVP antagonist and in dogs given both saralasin and the AVP antagonist, but there was no difference in the effect of AVP blockade alone vs. the effect of combined AVP and ANG II blockade. These data suggest that AVP, but not ANG II, is required for normal glucocorticoid and ACTH responses to hypotension. They also suggest that AVP is necessary for normal maintenance of arterial blood pressure and atrial pressures during NP infusion.

Reflex cardiovascular and respiratory effects of serotonin in conscious and anesthetized dogs.

Cardiovascular and respiratory effects of intra-left atrial or intra-left ventricular injection of serotonin were studied in conscious dogs (n = 8), anesthetized closed-chest dogs (n = 13) and anesthetized open-chest dogs (n = 9). Serotonin (50-200 microgram), injected as a bolus, resulted in an initial bradycardia and hypotension followed by a delayed tachycardia and hypertension in the conscious dogs. The hypertension was seen as an increase of 21.5 +/- 2.7 (mean +/ SE) mm Hg from a control pressure of 102.5 +/- 1.9 mm Hg, whereas the initial decrease in pressure was 22.6 +/- 1.9 mm Hg. The tachycardia was 23.3 +/- 3.9 beats/min above a control heart rate of 104.9 +/- 3.9 beats/min whereas the bradycardia was 58.5 +/- 3.7 beats/min below control. There was a significant attenuation of the hypotension in both groups of anesthetized dogs. In fact, no hypotension was elicited in the open-chest anesthetized dogs. Open-chest anesthetized dogs showed only a hypertensive response (mean increase 67.2 +/- 5.5 mm Hg). Stimulation of respiration was seen in all groups of dogs. In conscious dogs there was a 214.8 +/- 15.4% increase in respiratory depth and a 20.8 +/- 3.1 breaths/min increase in respiratory rate. Atropine significantly reduced the bradycardia and abolished the hypotension in conscious dogs. Bilateral cervical vagotomy did not abolish the response in open-chest anesthetized dogs. We conclude that the so-called "hypertensive coronary chemoreflex" is altered dramatically by the state of the preparation and by anesthesia.

Distribution of renal cortical blood flow during hemorrhagic hypotension in conscious dogs.

AbstractThe effect of hemorrhagic hypotension on distribution of renal cortical blood flow was investigated in 9 conscious dogs. 6 platinum electrodes were chronically implanted in inner and outer renal cortex and local cortical blood flow measured by hydrogen clearance. Urine was collected through a catheter implanted in the split bladder and total renal blood flow f RBF) determined by PAH clearance. In anesthetized dogs control blood flow averaged 3.72 ± 0.74 ml/min‐g in outer cortex and 3.60 ± 0.53 ml/rnin g in inner cortex. Local blood flow in conscious dogs fell to 30–60 % of control in the course of 11 days after implantation of the electrodes, though RBF was almost constant and filtering glomeruli were demonstrated in the small fibrotic zone (20–50 μ) close to the electrode tip. No change in local flow was found by induction of Nembutal anesthesia. Bleeding of conscious dogs 1–3 days after implantation, to mean arterial pressure 50 mm Hg, reduced local blood flow to 10–30 % of prebleeding control. The local blood flow in outer and inner cortex decreased near proportionately. Typically, flow at all electrode sites in outer and inner cortex showed a similar fall. A marked redistribution of cortical blood flow during hemorrhagic hypotension was never observed. Bilateral clamping of carotid arteries at normal and at low arterial pressures did not change outer or inner cortical blood flow.

Sympathetic and parasympathetic components of reflex tachycardia induced by hypotension in conscious dogs with and without heart failure.

The autonomic components of the reflex tachycardia following nitroglycerin and inferior vena caval occlusion (IVCO) were analysed in conscious, unsedated normal dogs and in dogs with congestive heart failure (CHF) before and after selective and combined beta-adrenergic and cholinergic blockades. In normal dogs nitroglycerin and IVCO decreased mean arterial pressure from 98 ± 1 to 69 ± 1 mmHg and 73 ± 2 mm Hg, respectively, while heart rate increased from 77 ± 3 to 176 ± 4 and 154 ± 6 beats/min (bpm), respectively. Selective beta-adrenergic or cholinergic blockades partially prevented the reflex tachycardia, while combined blockades abolished the reflex tachycardia. Thus, the reflex tachycardia following hypotension induced by either nitroglycerin or IVCO is mediated by a combination of sympathetic and parasympathetic influences.

Compensation to exsanguination hypotension in health conscious dogs.

In some earlier studies on exsanguination hypotension in conscious dogs, reduction in systemic arterial pressure to shock levels was accompanied by a transient tachycardia during the removal of blood, but the heart rate returned to level, at or near control values during extended periods with the mean arterial pressure between 40 and 60 mm Hg. This observation stimulated a series of experiments on five healthy conscious dogs in which transient hypotension was induced by withdrawing blood from the region of the right atrium to determine which mechanisms were dominant in the compensatory reaction. A surprising degree of variability in response was encountered, such that tachycardia was the main response on some occasions, increased peripheral resistance on others, and in still others, several mechanisms appeared to play a role. Similar variability in the response to exsanguination have been reported in human subjects. These observations suggest that the baroceptor reflexes are not simple servo controls and their role in everyday cardiovascular responses should be re-examined.