vasopressin--1-(1-mercaptocyclohexaneacetic-acid)-2-(o--methyl-l-tyrosine)-8-l-arginine- and Hypercapnia

In conscious dogs, arginine vasopressin (AVP) inhibits an angiotensin II drive to ventilation during air breathing and during acute hypercapnia. To determine whether AVP inhibits respiration in rats, as in dogs, respiration and metabolism were measured in six male Sprague-Dawley rats using a plethysmograph. Rats breathed air, followed by 5% and 6.5% CO2 with or without AVP V1 receptor block. In unblocked experiments, minute ventilation (V) increased to a comparable level during inhalation of both CO2 gas mixtures, resulting in a flattening of the ventilatory response to increased Paco2. However, oxygen consumption decreased during 6.5% CO2, compared with 5% CO2, so that the ventilatory equivalent for O2 increased in a more linear manner with respect to Paco2. The main effect of AVP V1 receptor block was to increase mean arterial blood pressure; there was no significant effect of AVP V1 receptor block on respiratory responses. AVP does not inhibit respiration in conscious rats as it does in conscious dogs.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Heart Rate; Hormone Antagonists; Hypercapnia; Male; Rats; Rats, Sprague-Dawley; Receptors, Vasopressin; Respiratory Physiological Phenomena

To evaluate the role of vasopressin in the renal changes during combined acute hypoxemia and acute hypercapnic acidosis, eight conscious female mongrel dogs prepared with controlled sodium intake at 80 meq/24 h for 4 days were studied in one of the following six protocols: acute hypoxemia (80 min, arterial PO2 34 +/- 1 mmHg) followed by combined acute hypoxemia and hypercapnic acidosis (40 min, arterial PO2 35 +/- 1 mmHg, arterial PCO2 58 +/- 1 mmHg, pH = 7.20 +/- 0.01) during 1) intrarenal vehicle at 0.5 ml/min (N = 8); or 2) intrarenal infusion of vasopressin V1-receptor antagonist [d(CH2)5Tyr(Me)]AVP at 5 ng.kg-1.min-1 (N = 5); and with normal gas exchange during 3) intrarenal vasopressin at 0.05 mU.kg-1.min-1 (N = 8); 4) simultaneous infusion of intrarenal vasopressin and [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N = 4); 5) intrarenal [d(CH2)5Tyr(Me)]AVP, 5 ng.kg-1.min-1 (N =4); and 6) intrarenal vehicle at 0.5 ml/min (N = 7). Intrarenal infusion of a subpressor dose of vasopressin resulted in a transient decrease in glomerular filtration rate and effective renal plasma flow over the first 20 min of infusion, suggesting that vasopressin induced nonsustained vasoconstriction of the renal vasculature. Intrarenal administration of [d(CH2)5Tyr-(Me)]AVP failed to block the fall in glomerular filtration rate or effective renal plasma flow when renal arterial blood vasopressin levels were elevated by intrarenal administration of exogenous vasopressin or by elevated systemic arterial endogenous circulating vasopressin during combined acute hypoxemia and hypercapnic acidosis. These data suggest that vasopressin (V1-receptor stimulation) does not play an important role in the renal vasoconstriction during combined acute hypoxemia and hypercapnic acidosis in conscious dogs.

Topics: Acidosis; Animals; Arginine Vasopressin; Dogs; Female; Hypercapnia; Hypoxia; Injections; Kidney; Receptors, Angiotensin; Receptors, Vasopressin; Reference Values; Renal Circulation; Vasopressins

Experiments were performed to test for a possible role of arginine vasopressin (AVP) in the renal vascular responses to the combination of hypoxia and varying levels of CO2 in the conscious rat. Animals were instrumented with pulsed Doppler flow probes on the left renal artery and with arterial and venous catheters. Renal blood flow (RBF) and mean arterial blood pressure (MABP) were determined in conscious, unrestrained rats under the following conditions: 1) hypocapnic hypoxia [arterial PO2 (PaO2) = 26 Torr; arterial PCO2 (PaCO2) = 21 Torr]; 2) isocapnic hypoxia (PaO2 = 34 Torr; PaCO2 = 36 Torr); 3) hypercapnic hypoxia (PaO2 = 42 Torr; PaCO2 = 57 Torr); and 4) room air control (PaO2 = 93 Torr; PaCO2 = 38 Torr). MABP fell from 104 +/- 2 to 83 +/- 5 mmHg during hypocapnic hypoxia but was unaffected by the other stimuli. RBF was significantly reduced by both hypocapnic and hypercapnic hypoxia and unchanged in the other protocols, whereas renal vascular resistance (RVR) was elevated only in the hypercapnic hypoxia group. Additional experiments were performed to test whether activation of V1-vasopressinergic receptors during hypoxia might mediate the observed changes in renal hemodynamics. Experiments were performed as before except that at the midpoint of hypoxic or room air exposure, 10 micrograms/kg of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP was administered. However, administration of the V1 antagonist had no effect on the observed renal hemodynamic responses to hypoxia. Therefore, although intense chemoreceptor stimulation by hypercapnic hypoxia may increase RVR and decrease renal perfusion, these renal hemodynamic responses do not appear to be mediated by increased circulating levels of AVP.

Topics: Animals; Arginine Vasopressin; Blood Vessels; Carbon Dioxide; Consciousness; Hemodynamics; Hypercapnia; Hypoxia; Oxygen; Rats; Rats, Inbred Strains; Renal Circulation

Experiments were performed to test the possible involvement of arginine vasopressin (AVP) in the systemic cardiovascular responses to acute hypercapnic acidosis in conscious chronically instrumented rats. Exposure to 6% CO2 caused arterial PCO2 to rise from 34 +/- 2 to 53 +/- 1 Torr. This level of hypercapnia was associated with a consistent bradycardia; however, cardiac output, blood pressure, and total peripheral resistance were not significantly affected. Administration of 10 micrograms/kg iv of the specific V1 vasopressinergic antagonist d(CH2)5Tyr(Me)AVP during 6% CO2 had no effect on any of the measured hemodynamic variables. Furthermore, d(CH2)5Tyr(Me)AVP also had no effect in normocapnic control animals. Exposure to a more severe level of hypercapnia (10% CO2, arterial PCO2 = 89 +/- 1 Torr) resulted in marked hemodynamic alterations. Profound bradycardia and decreased cardiac output in addition to increases in mean arterial blood pressure and total peripheral resistance were observed. V1 vasopressinergic antagonism during 10% CO2 had no effect on heart rate but greatly increased cardiac output. In addition, blood pressure fell and resistance was decreased below prehypercapnic levels. These data suggest that a number of the hemodynamic alterations associated with severe hypercapnic acidosis in the conscious rat may be mediated by the peripheral cardiovascular effects of enhanced AVP release.

Topics: Animals; Arginine Vasopressin; Blood Pressure; Carbon Dioxide; Cardiac Output; Heart Rate; Hypercapnia; Male; Partial Pressure; Rats; Rats, Inbred Strains; Vascular Resistance

Previous experiments have demonstrated that hypoxia stimulates the release of arginine vasopressin in conscious animals including the rat. The present study was designed to test whether AVP may exert a vasoconstrictor influence during hypoxia at varying levels of CO2. Systemic hemodynamics were assessed in conscious rats for 30 min under hypocapnic hypoxic, isocapnic hypoxic, hypercapnic hypoxic, and room air conditions. Progressive effects on heart rate (HR), cardiac output (CO), and total peripheral resistance (TPR) were observed with varying CO2 under hypoxic conditions. Hypocapnic hypoxia [arterial PO2 (PaO2) = 32 Torr; arterial PCO2 (PaCO2) = 22 Torr] caused HR and CO to rise and TPR to fall. Isocapnic hypoxia (PaO2 = 36 Torr; PaCO2 = 35 Torr) was associated with no significant changes in HR and CO or TPR, whereas hypercapnic hypoxia (PaO2 = 35 Torr; PaCO2 = 51 Torr) caused HR and CO to fall and TPR to rise. Room air time control experiments were associated with no change in measured hemodynamic variables. To determine the possible role of circulating AVP on these cardiovascular responses, additional experiments were performed where the specific V1-vasopressinergic antagonist d(CH2)5Tyr(Me)AVP (10 micrograms/kg iv) was administered at the midpoint of hypoxic exposure. Antagonist administration had no effect on hypocapnic hypoxic animals or animals breathing room air; however, blood pressure and TPR were significantly reduced by d(CH2)5Tyr(Me)AVP in both isocapnic and hypercapnic hypoxic animals. The heart rate response to hypoxia at the various CO2 levels was unaffected; however, cardiac output and stroke volume were increased after V1-antagonism in the isocapnic and hypercapnic hypoxic animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Arginine Vasopressin; Blood Pressure; Carbon Dioxide; Cardiac Output; Cardiovascular System; Heart Rate; Hypercapnia; Hypoxia; Male; Oxygen; Partial Pressure; Rats; Rats, Inbred Strains; Vascular Resistance

The physiological relationship of increased circulating angiotensin II and vasopressin to circulatory changes during combined hypoxemia and hypercapnic acidosis is unclear. To evaluate the role(s) of angiotensin II and vasopressin, seven unanesthetized female mongrel dogs with controlled sodium intake (80 meq/24 h X 4 d) were studied during 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2, 36 +/- 1 mmHg; PaCO2, 55 +/- 2 mmHg; pH = 7.16 +/- 0.04) under the following conditions: (a) intact state with infusion of vehicles alone; (b) beta-adrenergic blockade with infusion of d,l-propranolol (1.0 mg/kg bolus, 0.5 mg/kg per h); of the vasopressin pressor antagonist d-(CH2)5Tyr(methyl)arginine-vasopressin (10 micrograms/kg); and (d) simultaneous vasopressin pressor and angiotensin II inhibition with the additional infusion of 1-sarcosine, 8-alanine angiotensin II (2.0 micrograms/kg per min). The rise in mean arterial pressure during the combined blood-gas derangement with vehicles appeared to be related to increased cardiac output, since total peripheral resistance fell. Beta-adrenergic blockade abolished the fall in total peripheral resistance and diminished the rise in cardiac output during combined hypoxemia and hypercapnic acidosis, but the systemic pressor response was unchanged. In addition, the rise in mean arterial pressure during the combined blood-gas derangement was unaltered with vasopressin pressor antagonism alone. In contrast, the simultaneous administration of the vasopressin pressor and angiotensin II inhibitors during combined hypoxemia and hypercapnic acidosis resulted in the abrogation of the overall systemic pressor response despite increased cardiac output, owing to a more pronounced fall in total peripheral resistance. Circulating catecholamines were increased during the combined blood-gas derangement with vasopressin pressor and angiotensin II blockade, suggesting that the abolition of the systemic pressor response in the last 30 min of combined hypoxemia and hypercapnic acidosis was not related to diminished activity of the sympathetic nervous system. These studies show that vasopressin and angiotensin II are major contributors to the systemic pressor response during combined acute hypoxemia and hypercapnic acidosis.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Cardiac Output; Dogs; Female; Glucose; Heart Rate; Hemodynamics; Hypercapnia; Hypoxia; Propranolol; Saralasin; Stroke Volume; Vascular Resistance