Α‐adrenoceptors Can Mediate Chronotropic Responses in the Rat Heart

Flavahan, Nicholas A.; McGrath, J.C.

doi:10.1111/j.1476-5381.1981.tb16791.x

Cited by 49 publications

(20 citation statements)

References 17 publications

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“…Furthermore, the failure of prazosin to antagonize these right atrial rate responses, either in the unblocked state or in the presence of a high concentration of pindolol, was consistent with the response being mediated solely via f-adrenoceptors, with no aadrenoceptor involvement. Weak positive chronotropic responses mediated via a-adrenoceptors have been demonstrated with selective a-adrenoceptor agonists, but only in rat isolated atria (Wagner & Brodde, 1978;Chess-Williams & Broadley, 1987;Tung et al, 1987;Williamson & Broadley, 1987) and the pithed rat (Flavahan & McGrath, 1981;Tung et al, 1982). Closer inspection of the adrenaline concentration-response curves in the presence of pindolol indicates that prazosin may have displaced the lower portion of the curve, albeit slightly, which suggests that adrenaline may exert a minor positive chronotropic response through cx-adrenoceptors.…”

Section: Drugs Usedmentioning

confidence: 99%

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Williamson¹,

Broadley²

1989

British J Pharmacology

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1 The positive inotropic responses of rat paced left atria to adrenaline and noradrenaline were recorded. Desmethylimipramine (DMI, 1 gM) and metanephrine (IO gM) were initially present throughout. 2 The positive chronotropic responses of spontaneously beating right atria to adrenaline were used as a reference. In these, pindolol, in increasing concentrations, caused progressive shift of the concentration-response curves to the right, which yielded a pA2 value (8.15) compatible with antagonism of /-adrenoceptors. 3 The left atrial tension responses to adrenaline showed an initial progressive displacement by pindolol (up to 3gM) which gave an unexpectedly low pA2 value (6.48). However, with further increases in pindolol concentration there was no additional shift of the curve. In the presence of pindolol (3 jM), prazosin (O.1 M) displaced the curve to the right but the pA2 value derived from this shift (7.75) was less than expected for ax-adrenoceptor antagonism. 4 When the experiments in the presence of pindolol (3 jM) were repeated in the absence of DMI, prazosin displaced the concentration-response curves for adrenaline-induced left atrial tension to a greater extent and the pA2 value (8.76) was now compatible with adrenaline stimulating typical a -adrenoceptors. 5 The concentration-response curves for noradrenaline-induced left atrial tension were also progressively displaced to the right by pindolol (0.1, 0.3 and 1.OpM). These concentrations yielded a Schild plot of unity slope and a pA2 value of 7.94 + 0.04. This was not significantly different from the pA2 value of 8.02 + 0.07 determined for pindolol against isoprenaline in the left atria, which indicates a normal interaction of noradrenaline with P-adrenoceptors in the absence and presence of low concentrations of pindolol.6 A further increase in the concentration of pindolol to 3 gM failed to induce an additional shift of the noradrenaline curves, whether a 'before and after' antagonist or a 'naive tissue' design was adopted. Similarly, the rightwards shift of the concentration-response curves by timolol reached a limit as the concentration was increased. In all cases the limit of shift occurred at a noradrenaline EC50 value of 5-1O pM. 7 At the limit of JJ-adrenoceptor antagonism, prazosin and dibenamine did not displace the noradrenaline curves further. The residual inotropic response to noradrenaline therefore appeared to be mediated via neither a-nor f-adrenoceptors. 8 DMI, in the absence of fl-blockade, produced the potentiation of adrenaline and noradrenaline expected of a neuronal uptake inhibitor. However, in the presence of pindolol, there was no potentiation of the right atrial rate response to adrenaline while its left atrial tension responses were antagonized. This suggested that DMI was acting as an a-adrenoceptor antagonist. It also explained the less-than-expected shift by prazosin of the adrenaline responses in the presence of both pindolol and DMI, the latter drug already exerting some a-blocking activity. In contrast, the left atrial...

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Section: Drugs Usedmentioning

confidence: 99%

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Williamson¹,

Broadley²

1989

British J Pharmacology

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“…Perivascular pH can affect many cellular processes (4), but the precise mechanisms of vascular hyporesponsiveness remain uncertain. Low pH has been shown to reduce Ca 2+ influx (37), to inhibit myofilament contractility (38) and to alter receptors on the cell surface (39), accounting for the attenuation of vasoconstrictor responses.…”

Section: Metabolic Acidosismentioning

confidence: 99%

Effects of acid-base imbalance on vascular reactivity

Celotto

Capellini

Baldo

et al. 2008

Braz J Med Biol Res

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Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pH o ) and those occurring within the intracellular space (pH i ), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pH o , including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI 2 /cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

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“…Hiley, unpublished observations) and it has previously been shown that this heart rate response to phenylephrine is removed by the administration of prazosin (Hiley & Thomas, 1987). Also ar-adrenoceptors mediating tachycardia have been reported by Flavahan & McGrath (1981) and 89% for 15 and 30mlkg-1 respectively), whilst that to the hepatosplanchnic bed as a whole was greatest at the lowest respiratory volume (39% as compared with 17% and 155% for 20 and 30 ml kg-' respectively). Further, a significant decrease (32%) in the proportion of cardiac output passing to the epididimides was evident only at the respiratory volume of 30ml kg-1, whilst an increase in cardiac output distribution to the gastrointestinal tract was only seen at 15 ml kg-l (33%).…”

Section: Discussionmentioning

confidence: 98%

Effect of artificial respiratory volume on the cardiovascular responses to an α₁‐ and an α₂‐adrenoceptor agonist in the air‐ventilated pithed rat

MacLean¹

1988

British J Pharmacology

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1 The effect of varying artificial respiratory volume (at a fixed rate of 54 min-) on cardiac output, its distribution and tissue blood flows were determined with tracer microspheres in control pithed rats or during pressor responses to either the a1-adrenoceptor agonist phenylephrine or the a2-agonist xylazine. Phenylephrine was investigated in the presence of propranolol (3 mg kg 1). The rats were pithed under halothane anaesthesia. 2 A respiratory volume of 15 ml kg-produced modest hypercapnia (Paco2 = 47 mmHg), hypoxia (Pao2 = 60 mmHg) and acidosis (pH = 7.35) relative to control animals respired at 20 ml kg1 (Paco2 = 32 mmHg; Pao2 = 77 mmHg; pH = 7.47). In rats respired at 15 ml kg 1, total peripheral resistance was lower, and cardiac output greater (due to increased stroke volume), than in the controls. Lowering respiratory volume reduced distribution of cardiac output to the kidneys, increased it to the large intestine and also increased blood flow through the gastrointestinal tract, skin and spleen. A respiratory volume of 30 ml kg-1 gave mild hypocapnia (Paco2 = 19 mmHg), hyperoxia (Pao2 = 101 mmHg) and alkalosis (pH = 7.59) compared to 20 ml kg'-but had no effect on cardiac output distribution or organ blood flow although heart rate was 29% greater at 30 ml kg-'. 3 Xylazine (500 pg bolus followed by lOOI gmin1 infusion) at all three respiratory volumes gave well-sustained mean pressor responses of 62-64 mmHg by increasing both total peripheral resistance and cardiac output (resulting from increased stroke volume). It increased the proportion of cardiac output passing to the liver, reduced that going to the spleen and gastrointestinal tract and increased cardiac, renal and hepatosplanchnic blood flows. 4 The secondary, relatively sustained, pressor effect of phenylephrine (5 pg bolus followed by 0.4 pg min1 infusion, i.v.) varied at the 3 respiratory volumes with mean values from 32 to 53 mmHg. This response was due to both increased total peripheral resistance and cardiac output (resulting from greater stroke volumes and/or heart rates). Phenylephrine increased the proportion of cardiac output passing to the gastrointestinal tract, heart, kidneys and hepatosplanchnic bed and increased cardiac, hepatosplanchnic, renal and gastrointestinal blood flows. 5 Respiratory volume had no effect on the cardiovascular effects of xylazine. However, respiratory volume modified the effects of phenylephrine on heart rate and changed the relative contributions of stroke volume and heart rate to the increased cardiac output. It also influenced the effects of phenylephrine on cardiac output distribution to the liver, epididimides and hepatosplanchnic bed and on blood flow through skeletal muscle and the large intestine. 6 Changes in respiratory volume of air ventilated pithed rats thus influence cardiac output, its distribution and regional blood flows. Such changes can also differently influence the responses of various vascular beds to phenylephrine whilst having no effect on their responses to xylazine.

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Α‐adrenoceptors Can Mediate Chronotropic Responses in the Rat Heart

Cited by 49 publications

References 17 publications

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Effects of acid-base imbalance on vascular reactivity

Effect of artificial respiratory volume on the cardiovascular responses to an α₁‐ and an α₂‐adrenoceptor agonist in the air‐ventilated pithed rat

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Α‐adrenoceptors Can Mediate Chronotropic Responses in the Rat Heart

Cited by 49 publications

References 17 publications

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Do both adrenaline and noradrenaline stimulate cardiac α‐adrenoceptors to induce positive inotropy of rat atria?

Effects of acid-base imbalance on vascular reactivity

Effect of artificial respiratory volume on the cardiovascular responses to an α1‐ and an α2‐adrenoceptor agonist in the air‐ventilated pithed rat

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Product

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Effect of artificial respiratory volume on the cardiovascular responses to an α₁‐ and an α₂‐adrenoceptor agonist in the air‐ventilated pithed rat