Nimodipine inhibits the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb) in the rat

1998 ◽  
Vol 76 (10-11) ◽  
pp. 983-988 ◽  
Author(s):  
Francis Rioux ◽  
Mélanie St-Pierre ◽  
Nathalie Harvey ◽  
Steve Moisan ◽  
Kenneth E Burhop ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Calcium Channels ◽  
Calcium Antagonists ◽  
Pressor Response ◽  
Pressor Effect ◽  
Adrenoceptor Agonist ◽  
Pressor Activity ◽  
Tonic Phase ◽  
Diaspirin Crosslinked Hemoglobin

Impaired nitric oxide (NO) activity is associated with an increase in blood pressure in rats. Voltage-regulated calcium channels are believed to participate in this hemodynamic event. To further test this hypothesis, we examined the effect of nimodipine and verapamil (calcium antagonists) on the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a well-known NO scavenger, in anesthetized rats. Nimodipine, the most potent of the two calcium antagonists used, was also tested against phenylephrine (alpha1-adrenoceptor agonist). The pressor effect of DCLHb was reduced markedly by nimodipine and verapamil, whereas that elicited by phenylephrine, particularly the tonic phase of its pressor response, was resistant to blockade by nimodipine. The bradycardia and tachycardia associated with the pressor effects of DCLHb and phenylephrine, respectively, were not affected by nimodipine. The pressor effect elicited by DCLHb and its alteration by nimodipine were also examined in rats pretreated with 100% O2. This treatment was found to potentiate the pressor effect of DCLHb. However, this synergism did not impair the inhibitory action of nimodipine towards the pressor activity of DCLHb. Altogether these results suggest that the pressor activity of DCLHb in our animal model might involve the participation of voltage-regulated calcium channels.Key words: hemoglobin, nitric oxide, calcium channels, blood pressure, diaspirin-crosslinked hemoglobin.

Nonpeptide endothelin receptor antagonists attenuate the pressor effect of diaspirin-crosslinked hemoglobin in rat

1999 ◽  
Vol 77 (3) ◽  
pp. 188-194 ◽  
Author(s):  
Francis Rioux ◽  
Nathalie Harvey ◽  
Steve Moisan ◽  
Richard Larivière ◽  
Marcel Lebel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
No Synthase ◽  
Endothelin Receptor Antagonists ◽  
Pressor Effect ◽  
Endothelin Receptor ◽  
Hemodynamic Effects ◽  
Receptor Antagonists ◽  
Pressor Activity ◽  
Diaspirin Crosslinked Hemoglobin

Endothelin 1 (ET-1) is a potent vasoactive and mitogenic peptide that is thought to participate in the hemodynamic effects elicited by drugs that block the biosynthesis and release of endothelium-derived nitric oxide (NO), such as NO synthase inhibitors. Using the nonpeptide endothelin receptor antagonists bosentan and LU-135252, we tested the hypothesis that endothelins contribute to the pressor activity of diaspirin-crosslinked hemoglobin (DCLHb), a hemoglobin-based oxygen carrier, whose pressor activity in mammals is attributed primarily to a scavenging action towards NO. The NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME), ET-1, and noradrenaline (NA) were used as reference drugs. Bosentan markedly reduced the pressor effects elicited by DCLHb, L-NAME, and ET-1, but not those evoked by NA. LU-135252 attenuated the pressor effect elicited by DCLHb and ET-1, but not that produced by L-NAME or NA. The decreases in heart rate associated with the pressor effect of DCLHb and L-NAME were reduced by LU-135252, whereas only those elicited by DCLHb were attenuated by bosentan. In contrast with bosentan, LU-135252 caused a decrease in the baseline blood pressure and heart rate. These results suggest that endothelins may participate in the pressor activity of DCLHb. They suggest also that nonpeptide endothelin receptor antagonists such as bosentan or LU-135252 may be useful to counteract endothelin-mediated undesirable hemodynamic effects of drugs that inhibit the activity of the NO system.Key words: hemoglobin, endothelin, nitric oxide, blood pressure, diaspirin-crosslinked hemoglobin (DCLHb).

Mechanism of the acute pressor effect and bradycardia elicited by diaspirin crosslinked hemoglobin in anesthetized rats

1998 ◽  
Vol 76 (4) ◽  
pp. 434-442 ◽  
Author(s):  
Steve Moisan ◽  
Guy Drapeau ◽  
Kenneth E Burhop ◽  
Francis Rioux
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Heart Rate ◽  
Pressor Effect ◽  
Endogenous Nitric Oxide ◽  
Pressor Activity ◽  
Vagal Reflex ◽  
Generating System ◽  
Hypertensive Episode ◽  
Diaspirin Crosslinked Hemoglobin

Diaspirin crosslinked hemoglobin (DCLHb) is a chemically stabilizedhemoglobin (Hb) that induces an increase in blood pressure and a decrease of heart rate wheninjected intravenously in some animals. The mechanism by which DCLHb elicits thesehemodynamic effects was studied in pentobarbital-anesthetized, vagotomized rats using a varietyof drugs known for their inhibitory action towards endogenous hemodynamically active systems.The hypertensive episode elicited by DCLHb (100 or 400 mg·kg–1) was attenuatedin animals pretreated with NG-nitro-L-arginine (inhibitor of nitric oxidesynthases) throughout the 30-min period of observation, but it was not reduced in thosepretreated with a variety of sympatholytic drugs (e.g., prazosin), atropine, BIBP-3226(neuropeptide Y antagonist), indomethacin,[1-(Beta-mercapto-Beta,Beta-cyclopentanemethylene propionic acid), 2-(0-methyl)tyrosine]-Arg8 vasopressin (vasopressin antagonist), losartan (angiotensin antagonist),bosentan (endothelin antagonist), or L-arginine- (nitric oxide precursor), compared withcontrol animals. With the exception of propranolol and BIBP-3226, none of the aforenamedinhibitors reduced the amplitude of the bradycardia associated with the pressor effect of DCLHb.These results suggest that: (i) the acute (<30 min) pressor activity of DCLHb inour animal model requires the presence of an endogenous nitric oxide generating system to beexpressed; (ii) the bradycardia elicited by DCLHb might involve the participation ofneuropeptide Y and (or) its NPY-1 receptors, but it is unlikely to involve abaroreceptor-mediated vagal reflex, at least in our animal model.Key words: hemoglobin, nitric oxide, blood pressure, heart rate,DCLHb.

Comparison of fast and slow pressor effects of angiotensin II in the conscious rat

1981 ◽  
Vol 241 (3) ◽  
pp. H381-H388 ◽  
Author(s):  
A. J. Brown ◽  
J. Casals-Stenzel ◽  
S. Gofford ◽  
A. F. Lever ◽  
J. J. Morton
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pressor Response ◽  
Control Period ◽  
Urinary Sodium Excretion ◽  
Sodium Balance ◽  
Pressor Effect ◽  
Ang Ii ◽  
Conscious Rat ◽  
Female Wistar Rats

Female Wistar rats were infused intravenously with 5% dextrose for 3 days, then with angiotensin II (ANG II) in 5% dextrose at 20 ng . kg-1 . min-1 for 7 days, and finally with dextrose for 2.5 days. ANG II raised mean arterial pressure (MAP) gradually; by the 7th day it was 49.7 mmHg higher than during the dextrose control period in the same rats. Control rats were infused with dextrose for 12.5 days; MAP did not change. Plasma ANG II concentration was measured during infusion. In hypertensive rats on the 7th day of ANG II infusion, it was six times higher than in control rats infused with dextrose. Changes of blood pressure and plasma ANG II concentration were compared in further rats infused with much larger doses of ANG II. Rats receiving 270 ng . kg-1 . min-1 for 1 h had an almost maximal direct pressor response, MAP rising 45.3 mmHg and plasma ANG II rising 32-fold compared with controls. Thus, infusion of ANG II at low dose without direct pressor effect gradually raises blood pressure to a level similar to the maximum direct pressor effect produced by larger doses of ANG II. Sodium balance and food and water intakes were also measured and did not change during prolonged infusion of ANG II at 20 ng . kg-1 . min-1. Thus, the slow pressure effect of ANG II develops at a lower and more nearly physiological plasma concentration of the peptide than do the direct pressor effect and the effects on drinking, eating, and urinary sodium excretion.

Evidence that centrally released arginine vasopressin is involved in central pressor action of angiotensin II

1996 ◽  
Vol 270 (1) ◽  
pp. H167-H173 ◽  
Author(s):  
S. Lon ◽  
E. Szczepanska-Sadowska ◽  
M. Szczypaczewska
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Arginine Vasopressin ◽  
Pressor Response ◽  
Cardiovascular Effects ◽  
Pressor Effect ◽  
Ang Ii ◽  
Central Administration ◽  
Hypotensive Action ◽  
Series Of Experiments

Five series of experiments were performed on conscious trained dogs to find out whether intracranially released arginine vasopressin (AVP) is involved in mediation of central cardiovascular effects of angiotensin II (ANG II). The dogs were implanted with guide tubes leading to the third cerebral ventricle (ICV) and implanted with the intra-arterial catheters. Blood pressure and heart rate were continuously monitored during intracerebroventricular administration of 1) ANG II alone (250 ng), 2) AVP alone (0.01 ng/min during 10 min), 3) ANG II together with AVP, 4) AVP together with AVP V1-receptor antagonist 1(1-mercapto-4-methylcyclohexaneacetic acid)-8-AVP [MeCAAVP, V1ANT,100 ng/min], and 5) ANG II together with V1ANT. The results revealed that 1) ANG II and AVP applied separately elicited significant, long-lasting increases of blood pressure; 2) the maximum pressor effect after ANG II and AVP applied together did not differ from that after separate application of either of these peptides, but the duration of the pressor response was significantly shorter; 3) pretreatment with V1ANT effectively prevented blood pressure increases elicited by central administration of AVP and ANG II; and 4) after blockade of V1 receptors administration of AVP resulted in a significantly delayed decrease of blood pressure below baseline. The results strongly suggest that 1) centrally released AVP mediates the pressor effect of intracerebroventricularly applied ANG II by means of V1 receptors; 2) intracerebroventricularly applied ANG II and AVP interact to activate the mechanism involved in extinction of their pressor effect; and 3) blockade of central V1 receptors uncovers the hypotensive action of centrally applied AVP.

Pressor effect of arginine vasopressin in progressive autonomic failure

1986 ◽  
Vol 71 (2) ◽  
pp. 173-178 ◽  
Author(s):  
T. D. M. Williams ◽  
D. DaCosta ◽  
C. J. Mathias ◽  
R. Bannister ◽  
S. L. Lightman
Keyword(s):  
Blood Pressure ◽  
Arginine Vasopressin ◽  
Autonomic Failure ◽  
Pressor Response ◽  
Normal Subjects ◽  
Pressor Effect ◽  
Normal Volunteers ◽  
Pressor Responses ◽  
Transient Bradycardia ◽  
Related Increase

1. The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers. 2. Stepwise infusion of NA at rates of 300–3000 pmol min−1 kg−1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60–300 pmol min−1 kg−1. 3. Stepwise infusion of AVP at 0.2–5.0 pmol min−1 kg−1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000–4000 pmol/l, and still no significant pressor response was observed. 4. Stepwise infusion of AVP at 0.05–2.0 pmol min−1 kg−1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 ± 0.2 (mean ± se) to 30 ± 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 ± 1.8 pmol/l.

Calcium Antagonists Decrease Adrenal and Vascular Responsiveness to Angiotensin II in Normal Man

1981 ◽  
Vol 61 (s7) ◽  
pp. 65s-68s ◽  
Author(s):  
J. A. Millar ◽  
Kathleen McLean ◽  
J. L. Reid
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Pulse Rate ◽  
Calcium Antagonists ◽  
Pressor Response ◽  
Plasma Potassium ◽  
Normal Subjects ◽  
Rank Test ◽  
Vascular Responsiveness ◽  
Signed Rank Test

1. The effect of the calcium antagonist nifedipine on the pressor and aldosterone responses to angiotensin II was studied in six normal subjects. 2. Blood pressure, pulse rate and plasma aldosterone, potassium and cortisol were measured during paired consecutive infusions of angiotensin II (5, 10 and 20 ng min−1 kg−1) on two separate occasions. Nifedipine (20 mg by mouth) was given, 30 min before the second set of infusions. 3. After nifedipine there were reciprocal changes in supine resting blood pressure (−7 mm Hg) and pulse rate (+18 min−1) and a significant decrease in the pressor response to angiotensin II (P &lt; 0.05; Wilcoxon signed rank test). 4. Basal levels of aldosterone were not changed by nifedipine, but the response to angiotensin II was significantly attenuated (P &lt; 0.05). Nifedipine had no effect on plasma potassium or cortisol. 5. Transmembrane movement of calcium is involved in the aldosterone response to angiotensin II in man. Calcium antagonists may lower blood pressure via decreased adrenal responsiveness to angiotensin II as well as by peripheral vasodilatation.

Role of AVP in malignant DOC-salt hypertension: studies using vascular and antidiuretic antagonists

1987 ◽  
Vol 253 (5) ◽  
pp. F952-F958 ◽  
Author(s):  
J. Filep ◽  
J. C. Frolich ◽  
E. Foldes-Filep
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Plasma Renin Activity ◽  
Arginine Vasopressin ◽  
Pressor Response ◽  
Plasma Renin ◽  
Pressor Effect ◽  
Salt Hypertension ◽  
Freely Moving

To investigate the role of arginine vasopressin (AVP) in the maintenance of blood pressure in deoxycorticosterone (DOC)-salt hypertension, the effects of specific pressor and antidiuretic antagonists of AVP were studied in conscious, freely moving rats with established malignant DOC-salt hypertension. Plasma AVP level was significantly higher in hypertensive than in normotensive animals (4.8 +/- 1.0 vs. 2.0 +/- 0.3 fmol/ml, n = 5, P less than 0.02). Administration of d(CH2)5-d-Leu-VAVP, 10 micrograms/kg, an AVP antagonist that blocked the antidiuretic, but not the pressor effect of exogenous AVP, induced diuresis, and caused a transient fall in blood pressure from 173 +/- 3 to 167 +/- 4 mmHg (n = 8, P less than 0.01) with a concomitant slight increase in heart rate. Similar changes were observed after administration of d(CH2)5Tyr(Et)VAVP, 10 micrograms/kg, an antidiuretic plus pressor antagonist of AVP. Intravenous injection of d(CH2)5Tyr(Me)AVP, 10 micrograms/kg, a specific AVP pressor antagonist had no effect on blood pressure or heart rate, although it completely abolished the pressor response to exogenous AVP. Plasma renin activity remained suppressed following administration of all AVP antagonists. These findings suggest that if AVP should contribute to maintaining high blood pressure in malignant DOC-salt hypertension it would have to be the results of its antidiuretic and not its vasoconstrictor property.

Vasopressor and depressor actions of angiotensin in the anesthetized fowl

1982 ◽  
Vol 242 (3) ◽  
pp. H314-H324 ◽  
Author(s):  
H. Nishimura ◽  
Y. Nakamura ◽  
R. P. Sumner ◽  
M. C. Khosla
Keyword(s):  
Blood Pressure ◽  
Amino Acids ◽  
Smooth Muscle ◽  
Pressor Response ◽  
Pressor Effect ◽  
Ang Ii ◽  
6 Hydroxydopamine ◽  
Depressor Action ◽  
Biphasic Responses ◽  
Female Chicken

Vasopressor and depressor properties of angiotensins (ANG) were characterized in the anesthetized, adult female chicken Gallus gallus. [Asp1,Val5,Ser9]ANG I and [Asp1,Val5]ANG II (native fowl angiotensins) increased blood pressure, and removal or replacement of the amino acid in position 1 decreased pressor potency. The pressor effect of [Asp1,Val5]ANG II was inhibited nearly completely with [Sar1,Ile8]ANG II (5 micrograms.kg-1.min-1) and partially with [Sar1,Thr8]ANG II, [Ile8]ANG III, and [Ile8]ANG I. Phenoxybenzamine, reserpine, or 6-hydroxydopamine reduced the pressor action to one-third. After administration of these compounds [Asp1,Val5]ANG II caused biphasic responses, a depressor followed by a small pressor response. [Sar1,Ile8]ANG II completely, and meclofenamate partially, blocked the depressor response, whereas propranolol, methysergide, vasopressin antagonists, or atropine did not. These results suggest that in fowl 1) the first (Asp) and eighth (Phe) amino acids are important for receptor binding and action, 2) vasopressor action of angiotensin may be primarily caused by release of catecholamines, and 3) angiotensin may exert depressor action possibly by acting directly on the vascular smooth muscle.

scholarly journals THE INFLUENCE OF ETHER ANESTHESIA, OF HEMORRHAGE, AND OF PLETHORA FROM TRANSFUSION ON THE PRESSOR EFFECT OF MINUTE QUANTITIES OF EPINEPHRINE

1919 ◽  
Vol 29 (2) ◽  
pp. 173-186 ◽  
Author(s):  
Peyton Rous ◽  
George W. Wilson
Keyword(s):  
Blood Pressure ◽  
Pressor Response ◽  
Pressure Rise ◽  
Pressor Effect ◽  
Normal Height ◽  
Ether Anesthesia ◽  
Marked Influence ◽  
Low Blood Pressure ◽  
Small Doses ◽  
Considerable Period

Ether anesthesia has a marked influence in diminishing the pressor response to minute amounts of epinephrine injected directly into the circulation. Hemorrhage also acts to lessen or abolish the response, and to a degree directly proportional to the lowering of the blood pressure it causes. In the exsanguinated animal an amount of epinephrine three or four times that sufficient to produce a pressure rise of 10 to 15 mm. of mercury under normal conditions, may be entirely without effect. The response to large doses, on the other hand, is uninfluenced by ether or hemorrhage. The facts stated have a practical bearing not only on the employment of epinephrine to tide over collapse but on its possible utilization in the future to raise a low blood pressure to the normal height and maintain it during a considerable period. For the amount of epinephrine which under normal conditions will suffice to bring up the blood pressure may have little or no effect on an etherized individual or on one who has lost blood. The same difficulty will doubtless be encountered under other conditions. In animals rendered plethoric by transfusion the response to small doses of epinephrine lessens in proportion as the blood pressure is increased by the plethora.

Angiotensin II: nitric oxide interaction and the distribution of blood flow

1993 ◽  
Vol 265 (6) ◽  
pp. R1276-R1283 ◽  
Author(s):  
D. H. Sigmon ◽  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Blood Flow ◽  
Cardiac Output ◽  
Angiotensin Ii ◽  
Vascular Resistance ◽  
Total Peripheral Resistance ◽  
Pressor Response ◽  
Peripheral Resistance ◽  
Conscious Rats

Nitric oxide (NO) contributes to the regulation of regional blood flow. Inhibition of NO synthesis increases blood pressure and vascular resistance. Using radioactive microspheres and the substrate antagonist N omega-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) to block NO synthesis, we tested the hypothesis that there is a significant interaction between the vasodilator NO and the vasoconstrictor angiotensin II, which regulates regional hemodynamics. Further, we investigated the influence of anesthesia on this interaction. L-NAME increased blood pressure, decreased cardiac output, and increased total peripheral resistance in both anesthetized and conscious rats. In anesthetized rats, L-NAME decreased blood flow to visceral organs (i.e. kidney, intestine, and lung) but had little effect on blood flow to the brain, heart, or hindlimb. Treating anesthetized rats with the angiotensin II receptor antagonist losartan (10 mg/kg) attenuated the decrease in cardiac output and the increase in total peripheral resistance without affecting the pressor response to L-NAME. Losartan also attenuated the visceral hemodynamic responses to L-NAME. In conscious rats, L-NAME decreased blood flow to all organ beds. Treating these rats with losartan only marginally attenuated the increase in total peripheral resistance to L-NAME without significantly affecting the pressor response or the decrease in cardiac output. Losartan had no effect on the regional hemodynamic responses to L-NAME. These data suggest that NO-mediated vascular relaxation is an important regulator of total peripheral and organ vascular resistance. (ABSTRACT TRUNCATED AT 250 WORDS)

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