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

It has been observed that a vasopressin receptor antagonist attenuates hypoxic hyperemia in fetal sheep, whereas methionine enkephalin (Met) and leucine enkephalin (Leu) contribute to hypoxia-induced pial artery dilation in newborn pigs. This study was designed to investigate the relationship between vasopressin and opioids in hypoxia-induced pial artery dilation in the newborn pig by use of the closed cranial window technique. Hypoxia-induced pial artery dilation was attenuated during moderate [arterial Po2 (PaO2) approximately 35 mmHg] and severe hypoxia (PaO2 approximately 25 mmHg) by the vasopressin receptor antagonist, [beta-mercapto-beta beta-cyclopentamethylenepropionyl, 2-O-Me-Tyr2, Arg8]vasopressin (MeAVP, 5 micrograms/kg i.v.; 29 +/- 1 vs. 14 +/- 2 and 37 +/- 2 vs. 18 +/- 2% for moderate and severe hypoxia in absence vs. presence of MeAVP, respectively, n = 7). Hypoxia-induced dilation was accompanied by increased cerebrospinal fluid (CSF) vasopressin concentration (26 +/- 1 vs. 67 +/- 4 and 26 +/- 1 vs. 99 +/- 4 pg/ml for control vs. moderate and control vs. severe hypoxia, n = 5). Vasopressin increased CSF Met (895 +/- 28, 1,147 +/- 63, 1,327 +/- 48, and 1,600 +/- 75 pg/ml for control and 40, 400, and 4,000 pg/ml vasopressin, respectively, n = 7). CSF Leu concentration was similarly increased by vasopressin. Furthermore, MeAVP attenuated the release of Met during moderate hypoxia (910 +/- 38 and 2,682 +/- 49 vs. 911 +/- 38 and 2,110 +/- 84 pg/ml for control and moderate hypoxia in absence and presence of MeAVP, respectively, n = 5). MeAVP had similar effects on hypoxia-induced Leu release. These data show that vasopressin contributes to hypoxia-induced pial artery dilation and that vasopressin increases CSF Met and Leu concentrations. These data also suggest that elevated CSF vasopressin concentrations that occur during hypoxemia result in opioid release, which subsequently contributes to hypoxic pial artery dilation.

Topics: Animals; Arginine Vasopressin; Cerebral Arteries; Chromatography, High Pressure Liquid; Enkephalin, Leucine; Enkephalin, Methionine; Enkephalins; Female; Hormone Antagonists; Hypoxia; Male; Osmolar Concentration; Pia Mater; Radioimmunoassay; Vasodilation; Vasopressins

Exogenous vasopressin decreases blood flow to the choroid plexus and production of cerebrospinal fluid. Some studies indicate that hypoxia and increases in intracranial pressure (ICP) produce increases in circulating vasopressin. We examined the hypothesis that endogenous release of vasopressin decreases blood flow to the choroid plexus during hypoxia and increased ICP. Blood flow to the choroid plexus was measured in anesthetized rabbits using microspheres. Hypoxia increased cerebral blood flow more than twofold but had little effect on blood flow to the choroid plexus. In contrast, hypoxia produced a marked increase in blood flow to the choroid plexus in the presence of a vasopressin V1-antagonist, [d(CH2)5Tyr(Me)]AVP. During intracranial hypertension, blood flow to the choroid plexus decreased from 409 +/- 42 to 295 +/- 25 ml.min-1 x 100 g-1 (means +/- SE; P < 0.05 vs. control) when ICP was increased from 1 to 40 mmHg. The vasopressin antagonist inhibited the decrease in blood flow to the choroid plexus in response to increased ICP. Thus release of vasopressin during hypoxia and increased ICP have a constrictor effect on blood vessels of the choroid plexus. Plasma levels of vasopressin increased minimally during hypoxia and increased ICP, which suggests that sources of vasopressin other than plasma affect blood vessels of the choroid plexus. We propose that endogenous vasopressin may play a protective role during hypoxia and intracranial hypertension by a negative feedback mechanism to reduce blood flow to the choroid plexus.

Topics: Animals; Arginine Vasopressin; Choroid Plexus; Feedback; Hypoxia; Intracranial Pressure; Microspheres; Pseudotumor Cerebri; Rabbits; Regional Blood Flow; Vasopressins

1. In spontaneously breathing rats anaesthetized with Saffan, we have investigated the role of vasopressin in the cardiovascular responses evoked by systemic hypoxia (breathing 8 or 6% O2 for 5 min). 2. Breathing 8% O2 evoked an increase in respiratory frequency and tidal volume; arterial O2 pressure (Pa,O2) fell to 37 mmHg and arterial CO2 pressure (Pa,CO2) fell to 30 mmHg. Concomitantly, there was a fall in arterial pressure, tachycardia and increases in femoral and renal vascular conductances indicating net vasodilatation in skeletal muscle and kidney. The vasopressin V1-receptor antagonist, d(CH2)5Tyr(Me)-arginine vasopressin (20 micrograms kg-1 i.v.), had no significant effect on the baseline values of any recorded variables, nor on the respiratory or blood gas changes evoked by 8% O2. However, it accentuated the fall in arterial pressure and the increase in femoral vascular conductance (+22 vs. +77% at the 5th minute) produced by 8% O2, but had no significant effect on the increase in renal vascular conductance. 3. Breathing 6% O2 evoked qualitatively similar responses as 8% O2 but Pa,O2 fell to 33 mmHg and Pa,CO2 fell to 28 mmHg and the respiratory and cardiovascular changes tended to be larger than those evoked by 8% O2. Again the V1-receptor antagonist accentuated the hypoxia-induced fall in arterial pressure and increase in femoral vascular conductance (+5 vs. +76% at the 5th minute). 4. Infusion of vasopressin (1.5 ng min-1 kg-1 i.v.) for 5 min with the aim of producing a plasma concentration comparable to that reached during 8% O2, induced a rise in arterial pressure (9%), bradycardia (-5%) and a decrease in femoral (-11%) and renal vascular conductance (-4%). 5. These results suggest that vasopressin released during hypocapnic hypoxia helps to limit the evoked fall in arterial pressure by exerting a vasoconstrictor influence on skeletal muscle.

Topics: Anesthesia; Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Blood Pressure; Heart; Hemodynamics; Hypothalamus; Hypoxia; Male; Rats; Rats, Wistar; Regional Blood Flow; Respiration; Vasopressins

1. In rats anaesthetized with Saffan, the spinotrapezius muscle was prepared for in vivo microscopy. Systemic hypoxia (breathing 8% O2 for 3 min) induced a fall in arterial pressure and tachycardia, together with constriction in some arterioles and venules of each section of the vascular tree and dilatation in others. 2. The vasopressin V1-receptor antagonist d(CH2)5Tyr(Me)-arginine vasopressin (20 mg kg-1 I.V.) preferentially attenuated constrictor responses induced by hypoxia in both arterioles and venules, but had no significant effect on the dilator responses. Analysis of responses in individual sections of the vascular tree suggested that the V1-receptor antagonist reduced hypoxia-induced constrictor responses in proximal arterioles (> 13 microns diameter) though not in terminal arterioles (< 13 microns), but reduced hypoxia-induced constrictor responses in both the proximal and distal venules (9-130 microns). 3. Infusion of vasopressin at 1.4, 2.8, 5.7 and 11.4 ng min-1 kg-1 i.v. for 3 min, expected to produce plasma concentrations within the range 28-228 pg ml-1, evoked rises in arterial pressure together with decreases in heart rate. There was also vasoconstriction in the proximal arterioles of spinotrapezius that was graded with vasopressin concentration (5-35% decrease in diameter). 4. Infusion of vasopressin at 1.4 mg min-1 kg-1 i.v. for 3 min with the intention of producing a plasma concentration likely to be reached or exceeded during 8% O2, evoked constriction of all proximal arterioles, though not of terminal arterioles, and constriction of all venous vessels. The magnitude of the constriction induced by vasopressin in vessels that dilated during hypoxia was just as great as in those that constricted during hypoxia. 5. We propose that vasopressin released during systemic hypoxia exerts a constrictor influence upon the proximal arterioles and all sections of the venous tree of skeletal muscle. In individual arterioles and venules the constrictor influence of vasopressin and catecholamines may be overcome by the influence of locally released vasodilator metabolites.

Topics: Animals; Antidiuretic Hormone Receptor Antagonists; Arginine Vasopressin; Arterioles; Blood Pressure; Heart Rate; Hypoxia; Infusions, Intravenous; Male; Muscles; Rats; Rats, Wistar; Vasoconstriction; Vasopressins; Venules

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

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