Pressor action of beta blocking agents in rats

1970 ◽  
Vol 48 (7) ◽  
pp. 481-489 ◽  
Author(s):  
D. Regoli
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Beta Blockers ◽  
Receptor Blockade ◽  
Pressor Effect ◽  
Blocking Agents ◽  
Beta Blocking ◽  
Endogenous Catecholamines ◽  
Beta Receptors ◽  
Alpha Receptors

Propranolol (10 to 30 μg/kg), oxprenolol (trasicor) (5 to 10 μg/kg), and sotalol (10 to 50 μg/kg) evoke an acute and prolonged increase of arterial pressure in normal and nephrectomized rats, while after adrenalectomy the arterial pressure remains unchanged or is reduced. The pressor effect is accompanied by a reduction of heart rate. The dose of the three beta blockers evoking an arterial pressure increase does not antagonize the effect of isopropylnoradrenaline. To block the beta receptors, doses 10 to 100 times higher than those effective on arterial pressure have to be used. The block of the beta receptors is accompanied by an initial fall of the blood pressure and by a significant decrease of the heart rate. The pressor effect of beta blockers is not antagonized but rather is potentiated by phenoxybenzamine and phentolamine. Moreover, in the presence of an alpha receptor blockade, the administration of beta blockers partially restores the response to catecholamines. These results support the hypothesis that the pressor effect evoked by beta receptor blocking agents may be due: (a) to the release of endogenous catecholamines and (b) to the interference by beta blockers with phenoxybenzamine and phentolamine on the alpha receptors.

Pressor Effect of Beta Blocking Agents in Rats

1972 ◽  
Vol 50 (3) ◽  
pp. 207-214 ◽  
Author(s):  
D. Regoli ◽  
U. Regoli ◽  
E. Gysling
Keyword(s):  
Blood Pressure ◽  
Arterial Pressure ◽  
Vascular System ◽  
Beta Blockers ◽  
Smooth Muscles ◽  
Pressor Effect ◽  
Alpha Blockers ◽  
Blocking Agents ◽  
Biphasic Effect ◽  
Small Doses

In rats anesthetized with urethane, intravenous injection of oxprenolol, propranolol, and d-propranolol increases arterial pressure, while practolol is ineffective. These changes of arterial pressure occur in rats previously treated with phentolamine or phenoxybenzamine, indicating that the pharmacological block of alpha receptors does not prevent vasoconstriction by oxprenolol and propranolol. On the contrary, beta receptor blocking agents have little effect on the arterial pressure of rats treated with a ganglion blocker (pentolinium).The pressor action of adrenaline and angiotensin is significantly depressed by alpha blockers, but small doses of oxprenolol restore completely the action of angiotensin and, in part, that of adrenaline. Adrenaline produces a biphasic effect on the blood pressure of anesthetized rats. Both phases of the effect are eliminated by alpha blockers while ganglion blocker abolishes the hypotensive phase only. Administration of small doses of oxprenolol and propranolol (1–10 μg/kg) in untreated rats or in animals treated with alpha blockers increases significantly the blood pressure, but does not modify the biphasic effect of adrenaline.The results indicate that the pressor effect of small doses of beta blocker may not be entirely related to the elimination of the beta inhibitory effect of exogenous adrenaline on the vascular system. No changes of blood pressure occur when beta blockers are administered to animals treated with ganglion blockers, suggesting that the vasoconstriction produced by propranolol and oxprenolol is not due to a direct effect on the vascular smooth muscles.

CATECHOLAMINE ANTAGONISM TO OXYTOCIN-INDUCED MILK-EJECTION

1971 ◽  
Vol 68 (1_Suppla) ◽  
pp. S5-S38 ◽  
Author(s):  
Helmuth Vorherr
Keyword(s):  
Receptor Blockade ◽  
Milk Ejection ◽  
Beta Adrenergic ◽  
Beta Receptor ◽  
Beta Receptors ◽  
Alpha Receptors ◽  
Adrenergic Blockers ◽  
Beta Receptor Blockade ◽  
Second Pain ◽  
Stimulation Of

ABSTRACT In lactating rats and rabbits the mode of antagonism of sympathomimetics, angiotensin or pain toward oxytocin-induced milk-ejection was investigated. In rats intra-arterial (intrafemoral) doses of 0.01–0.02 μg or intravenous (iv) doses of 0.1–0.5 μg of either epinephrine, isoproterenol, norepinephrine, angiotensin or 10 μg of phenylephrine injected simultaneously with, or 30 seconds before an oxytocin dose (10 μU intrafemoral, 300 μU iv) greatly inhibited or suppressed the oxytocin response. A 15 second pain stimulus caused moderate inhibition. With alpha-receptor blockade pain, epinephrine, isoproterenol, norepinephrine, phenylephrine and angiotensin inhibition were, respectively, 70%, 75%, 100%, 40%, 0% and 100%. Under beta-receptor blockade the corresponding values were 14%, 40%, 0%, 70%, 100% and 100%; with simultaneous intrafemoral injections neither catecholamine was inhibitory toward oxytocin. In corresponding rabbit experiments approximately 10-fold higher iv drug dosages were applied and similar results were observed. In both species, combined alpha and beta-receptor blockade nearly eliminated the antagonistic actions of sympathomimetics toward oxytocin, whereas angiotensin inhibition persisted unchanged. The results indicate: 1) Mammary myoepithelial cells contain beta-adrenergic receptors but no alpha-receptors; 2) Inhibition of oxytocin-induced milk-ejection by isoproterenol and phenylephrine is meditated through stimulation of myoepithelial beta-receptors (myoepithelial relaxation) and vascular alpha-receptors (vasoconstriction), respectively; 3) Epinephrine and norepinephrine inhibition of milk-ejection is due to stimulation of vascular alpha-receptors and myoepithelial beta-receptors; 4) Angiotensin effects are unrelated to adrenergic receptor mechanisms; 5) Administration of both alpha and beta-adrenergic blockers is desirable for stabilizing the sensitivity of the oxytocin milk-ejection assay preparation against interference from endogenous or exogenous catecholamines; 6) Other than using adrenergic blockers, pharmacologic doses of oxytocin can correct nursing difficulties in animals and man with hyperfunction of the adrenal-sympathetic system.

Haemodynamic Effects of Different Beta Blockers in Angina Pectoris

1977 ◽  
Vol 22 (1) ◽  
pp. 64-68 ◽  
Author(s):  
H. Åström ◽  
B. Jonsson
Keyword(s):  
Heart Rate ◽  
Angina Pectoris ◽  
Stroke Volume ◽  
Partial Agonist ◽  
Beta Blockers ◽  
Haemodynamic Effects ◽  
Agonist Activity ◽  
Peripheral Vascular ◽  
Reduce Heart Rate ◽  
Beta Blocking

Beta-blocking agents with partial agonist activity seem to reduce heart rate at rest slightly less than those without this property. Cardio-selective drugs have no effect on stroke volume at rest contrary to the non-selective ones which will reduce it somewhat. This difference is abolished during exercise. The only difference seen during work between different beta-blockers is the effect on the peripheral vascular resistance. The selective drugs lower the arterial pressure with unchanged resistance.

Glycine microinjected into nucleus tractus solitarii of rat acts through cholinergic mechanisms

1991 ◽  
Vol 260 (4) ◽  
pp. H1326-H1331 ◽  
Author(s):  
W. T. Talman ◽  
J. M. Colling ◽  
S. C. Robertson
Keyword(s):  
Heart Rate ◽  
Nmda Receptor ◽  
Arterial Pressure ◽  
Cardiovascular Responses ◽  
Cardiovascular Regulation ◽  
Nucleus Tractus Solitarii ◽  
Receptor Blockade ◽  
Receptor Complex ◽  
Cholinergic Mechanisms ◽  
Nmda Receptor Complex

Previous studies have demonstrated the release of glycine from neurotransmitter pools in the region of the nucleus tractus solitarii (NTS) where cardiovascular afferents terminate. Microinjection of glycine into NTS elicits decreases in arterial pressure and heart rate; these effects are also produced by glutamate or acetylcholine. As glycine may act both at the N-methyl-D-aspartate (NMDA)-receptor complex and centrally to release acetylcholine, we have sought to determine whether the cardiovascular responses to exogenous glycine are mediated through glutamatergic or cholinergic mechanisms. Responses to glycine microinjected into the NTS of anesthetized rats were not affected by blockade of the NMDA receptor complex but, like acetylcholine, were blocked by muscarinic receptor blockade. Physostigmine prolonged responses to glycine. Subthreshold doses of glycine, which augmented responses to acetylcholine microinjected into NTS, either decreased or had no effect on glutamate or NMDA. This study supports a role for glycine in cardiovascular regulation by the NTS and suggests that the actions of glycine may be effected, at least in part, through cholinergic mechanisms.

Profound Increase in Epinephrine Concentration in Plasma and Cardiovascular Stimulation after [micro sign]-Opioid Receptor Blockade in Opioid-addicted Patients during Barbiturate-induced Anesthesia for Acute Detoxification 

1998 ◽  
Vol 88 (5) ◽  
pp. 1154-1161 ◽  
Author(s):  
Peter Kienbaum ◽  
Norbert Thurauf ◽  
Martin C. Michel ◽  
Norbert Scherbaum ◽  
Markus Gastpar ◽  
...  
Keyword(s):  
Heart Rate ◽  
Cardiac Index ◽  
Arterial Pressure ◽  
Opioid Receptor ◽  
Resistance Index ◽  
Systolic Arterial Pressure ◽  
Mu Opioid Receptor ◽  
Receptor Blockade ◽  
Mu Opioid ◽  
A Minor

Background Acute displacement of opioids from their receptors by administration of large doses of opioid antagonists during general anesthesia is a new approach for detoxification of patients addicted to opioids. The authors tested the hypothesis that mu-opioid receptor blockade by naloxone induces cardiovascular stimulation mediated by the sympathoadrenal system. Methods Heart rate, cardiac index, and intravascular pressures were measured in 10 patients addicted to opioids (drug history; mean +/- SD, 71 +/- 51 months) during a program of methadone substitution (96 +/- 57 mg/day). Cardiovascular variables and concentrations of catecholamine in plasma were measured in the awake state, during methohexital-induced anesthesia (dose, 74 +/- 44 microg x kg(-1) x min(-1)) before administration of naloxone, and repeatedly during the first 3 h of mu-opioid receptor blockade. Naloxone was administered initially in an intravenous dose of 0.4 mg, followed by incremental bolus doses (0.8, 1.6, 3.2, and 6.4 mg) at 15-min intervals until a total dose of 12.4 mg had been administered within 60 min; administration was then continued by infusion (0.8 mg/h). Results Concentration of epinephrine in plasma increased 30-fold (15 +/- 9 to 458 +/- 304 pg/ml), whereas concentration of norepinephrine in plasma only increased to a minor extent (76 +/- 44 to 226 +/- 58 pg/ml, P < 0.05). Cardiac index increased by 74% (2.7 +/- 0.41 to 4.7 +/- 1.7 min(-1) x m(-2)), because of increases in heart rate (89 +/- 16 to 108 +/- 17 beats/min) and stroke volume (+44%), reaching maximum 45 min after the initial injection of naloxone. In parallel, systemic vascular resistance index decreased (-40%). Systolic arterial pressure significantly increased (113 +/- 16 to 138 +/- 16 mmHg), whereas diastolic arterial pressure did not change. Conclusions Despite barbiturate-induced anesthesia, acute mu-opioid receptor blockade in patients addicted to opioids induces profound epinephrine release and cardiovascular stimulation. These data suggest that long-term opioid receptor stimulation changes sympathoadrenal and cardiovascular function, which is acutely unmasked by mu-opioid receptor blockade. Because of the attendant cardiovascular stimulation, acute detoxification using naloxone should be performed by trained anesthesiologists or intensivists.

Pronethalol

1964 ◽  
Vol 2 (12) ◽  
pp. 45-46
Keyword(s):  
Heart Rate ◽  
Blood Vessels ◽  
Ergot Alkaloids ◽  
Force Of Contraction ◽  
Beta Receptors ◽  
Alpha Receptors ◽  
Heart Disorders

Adrenaline acts on two kinds of receptors, alpha and beta receptors. Constriction of blood vessels by adrenaline is due to occupation of alpha receptors, and dilatation of blood vessels and increase in heart rate and force of contraction to occupation of beta receptors. Noradrenaline and isoprenaline are relatively more selective than adrenaline: noradrenaline produces predominantly alpha effects, isoprenaline largely beta effects. Alpha or beta receptors may be blocked selectively by suitable drugs. Drugs which block alpha receptors have been known for some time: they include several ergot alkaloids, phentolamine and phenoxybenzamine. The first drug developed to block beta receptors was dichloroisoprenaline, but it was not used clinically because it also has sympathomimetic activity. More recently another derivative of isoprenaline, pronethalol (Alderlin - ICI), has been introduced and tried in a number of heart disorders.

Bradykinin contributes to the exercise pressor reflex: mechanism of action

1993 ◽  
Vol 75 (5) ◽  
pp. 2061-2068 ◽  
Author(s):  
H. L. Pan ◽  
C. L. Stebbins ◽  
J. C. Longhurst
Keyword(s):  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Left Ventricular Pressure ◽  
Muscle Afferents ◽  
Left Ventricular ◽  
Receptor Blockade ◽  
Exercise Pressor Reflex ◽  
Pressor Reflex ◽  
Over Time

This study determined the receptors responsible for mediating bradykinin's effect on skeletal muscle afferents that cause the pressor reflex in anesthetized cats. In eight cats, 1 microgram of bradykinin was injected intra-arterially into the gracilis muscle before and after intravenous injection of a kinin B2-receptor antagonist (NPC 17731, 20 micrograms/kg). Initial injection of bradykinin reflexly increased mean arterial pressure by 23 +/- 7 mmHg, maximal change in pressure over time by 439 +/- 272 mmHg/s, and heart rate by 11 +/- 4 beats/min. The hemodynamic response to bradykinin was abolished by kinin B2-receptor blockade. Similar injection of the kinin B1-receptor agonist des-Arg9-bradykinin caused no cardiovascular responses (n = 6). In eight different animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses to 30 s of electrically stimulated hindlimb contraction were attenuated by 50 +/- 6, 55 +/- 7, and 41 +/- 8%, respectively, after kinin B2-receptor blockade. In eight other animals, mean arterial pressure, maximal change in left ventricular pressure over time, and heart rate responses were reduced by 58 +/- 8, 66 +/- 6, and 40 +/- 12%, respectively, after inhibition of prostaglandin synthesis with indomethacin (2.5–3 mg/kg iv) and were then abolished by subsequent B2-receptor blockade. These data suggest that bradykinin contributes to the exercise pressor reflex through its action on kinin B2 receptors located on the nerve endings of the muscle afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

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