The effects of arterial blood gas tensions on pressor responses to angiotensin II in the pithed rat.

Grant, T.; McGrath, J.C.

doi:10.1113/jphysiol.1986.sp016018

Cited by 5 publications

(11 citation statements)

References 6 publications

(13 reference statements)

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“…Since vascular tone in the pithed rat (mainly venous) seems to be maintained by a high circulating level of angiotensin II (Kaufman & Vollmer, 1985;Grant & McGrath, unpublished) and since the pressor response to intravenous infusion of exogenous angiotensin II is blocked by the dose of nifedipine used in the current study (Grant & McGrath, 1984), we expected that nifedipine would reduce arterial blood pressure by blocking the effects ofendogenous angiotensin: blocking the venomotor effect of endogenous angiotensin II reduces venous return and hence cardiac output, thus decreasing arterial blood pressure. Consequently, any vasopressor response caused by an increase in peripheral resistance, to whatever stimulus, should be reduced since such responses are proportional to the initial arterial blood pressure.…”

Section: Discussionmentioning

confidence: 93%

“…The responses mediated by agonists which are selective for the two receptors can be differentially modulated by a variety of factors including blood gases, angiotensin converting enzyme inhibitors and calcium channel blockers (Flavahan & McGrath, 1981;Van Meel et al, 1981;McGrath et al, 1982;Grant & McGrath, 1984;O'Brien et al, 1985). ' Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

“…The pithed rat has been used to demonstrate the two subtypes of x-adrenoceptor which mediate pressor responses and are presumably located on the smooth muscle of resistance arteries and/or arterioles (Drew & Whiting, 1979;Docherty & McGrath, 1980a). The responses mediated by agonists which are selective for the two receptors can be differentially modulated by a variety of factors including blood gases, angiotensin converting enzyme inhibitors and calcium channel blockers (Flavahan & McGrath, 1981;Van Meel et al, 1981;McGrath et al, 1982;Grant & McGrath, 1984;O'Brien et al, 1985). ' Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

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Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

McGrath

O'Brien

1987

British J Pharmacology

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1 Nifedipine was tested against pressor responses in the pithed rat to ten agonists with varying selectivity for a,-and a2-adrenoceptors, injected as a bolus or infused intravenously: i.e. amidephrine, azepexole, cirazoline, indanidine, M7, methoxamine, noradrenaline (NA), oxymetazoline, phenylephrine and xylazine. Nifedipine, administered before the agonists, inhibited responses initiated by all agonists, usually for both the bolus and infusion responses. 2 With a bolus, blockade was significantly greater against the more prolonged, secondary components of the pressor responses. This demonstrates that calcium-entry occurs during the secondary component of the a-adrenoceptor-mediated response and can be initiated by either a,-or 2-adrenoceptor subtypes.3 The time courses of responses to infusion varied. Selective a,-adrenoceptor agonists, with the exception of indanidine, did not produce a stable pressor response during the 20 min infusion time but M2-adrenoceptor agonists did. Nifedipine reduced responses to infusion with no preference for a,-or a2-agonists. Phenylephrine and NA produced pressor responses which reached a peak and then declined during the remainder of the infusion. 4 The levels ofNA in arterial and venous plasma were measured by h.p.l.c. during the infusion ofNA. Arterial NA levels rose throughout the infusion whereas venous levels remained relatively unaffected. The absolute levels of plasma NA suggest that a large proportion of intravenously administered NA is removed in the pulmonary circulation and the remainder is removed in the systemic circulation with negligible recirculation. 5 The consequences of these results, for assessment of the mechanisms of action of adrenoceptor agonists and calcium entry blockers, are discussed.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

McGrath

O'Brien

1987

British J Pharmacology

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“…In the pithed rat, the pressor response to angiotensin II can be blocked by nifedipine (Grant & McGrath, 1984b) and so part of the inhibitory effect of nifedipine on the prolonged pressor response to aagonists may be due to interference with a permissive effect of angiotensin II.…”

Section: The Effect Ofenalapril On Cardiovascular Changes Induced By mentioning

confidence: 99%

Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α₁‐ and α₂‐adrenoceptor agonists in pithed normotensive rats

MacLean

1988

British J Pharmacology

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1 Cardiac output, its distribution and regional vascular resistances were determined with tracer microspheres in pithed rats in the presence of the angiotensin converting enzyme inhibitor enalapril.The effects of enalapril on the cardiovascular responses elicited by either the ax-adrenoceptor agonist phenylephrine or the a2-adrenoceptor agonist xylazine were determined. 2 Enalapril decreased diastolic and mean blood pressure by decreasing cardiac index and total peripheral resistance. It induced vasodilatation in the kidney, epididimides, epididimidal fat and pancreas/mesentery. Vasoconstriction in the lungs, testes and liver was evident following enalapril administration as well as a decrease in the proportion of cardiac output passing to them, whilst the pancreas and mesentery received a greater proportion of the cardiac output. All the above effects of enalapril were reversed by infusion of angiotensin II at a rate of 75 ng kg-l minm .3 Xylazine increased blood pressure by increasing both cardiac output and total peripheral resistance. Enalapril did not affect the increase in cardiac output caused by xylazine but decreased the effect of the a2-agonist on blood pressure by preventing the increase in total peripheral resistance. Inhibition by enalapril of xylazine-induced vasoconstriction in the kidneys, testes, fat and gastrointestinal tract contributed to the decrease in total peripheral resistance. Enalapril also inhibited xylazine-induced changes in cardiac output distribution to the liver, lungs and heart. All the above effects of enalapril were reversed by infusion of angiotensin II. 4 Enalapril decreased the sustained phase of the pressor response to an infusion of phenylephrine whilst having no effect on the initial peak pressor response to a bolus injection of phenylephrine. Phenylephrine increased both cardiac output and total peripheral resistance and enalapril abolished its effect on total peripheral resistance whilst having no effect on the increase in cardiac output. Enalapril inhibited phenylephrine-induced vasoconstriction in the testes, fat, muscle, spleen and gastrointestinal tract. Enalapril also inhibited phenylephrine-induced changes in cardiac output distribution to the lungs and liver. The infusion of angiotensin II did not fully reverse the inhibitory effect of enalapril either on the phenylephrine-induced increases in diastolic blood pressure or on the vasoconstriction in the fat, spleen and gastrointestinal tract, but did reverse all other effects of enalapril.5 It is concluded that, although enalapril does not affect the increases in cardiac output caused by xylazine and phenylephrine, it inhibits the pressor responses to these agonists by reducing the resistance changes which they induce in several vascular beds. Vasoconstriction induced by xylazine may be mediated by circulating angiotensin II, as xylazine had a vasoconstrictor action in vascular beds devoid of a2-adrenoceptors mediating vasoconstriction. It is also concluded that, since endogenous angiotensin II facilitates the s...

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“…For example blood gases had differential effects not only be tween a-adrenoceptor sub-types but on re sponses to angiotensin II (All) [11][12][13], and All itself exerted differential effects on re sponses to different a-adrenoceptor subtypes [14]. Thus, in seeking to study the physiological functional responses mediated by the a-adrenoceptor sub-types, the possi ble contributions from various factors present in the cellular environment should be considered.…”

Section: Introductionmentioning

confidence: 99%

Physiological Modulation of α-Adrenoceptor and 5HT Receptor Expression in Blood Vessels

McGrath

Dunn²,

Templeton³

1990

J Vasc Res

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In vitro experiments on vascular smooth muscle often fail to reveal phenomena clearly demonstrable in vivo. Several recent observations in our laboratory have revealed the facility to uncover responses mediated by receptors whose functional expression had remained hidden with the standard experimental conditions first employed: conversely manipulation of conditions can selectively hide a particular receptor’s response. Examples include the uncovering of responses to: 5HT₁ receptors by raised O₂ tension (via cyclooxygenase products) in human umbilical vessels; α₂-adrenoceptors in rabbit saphenous artery by angiotensin II and α₂-adrenoceptors in perfused rat tail by elevating tone with vasopressin. The powerful synergism of agonists which cannot on their own cause contraction, can lead to inaccurate interpretations of agonist-antagonist interactions. Finally, the influence of tissue metabolism on receptor expression clearly illustrates the complex processes which must be involved in vivo.

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The effects of arterial blood gas tensions on pressor responses to angiotensin II in the pithed rat.

Cited by 5 publications

References 6 publications

Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α₁‐ and α₂‐adrenoceptor agonists in pithed normotensive rats

Physiological Modulation of α-Adrenoceptor and 5HT Receptor Expression in Blood Vessels

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The effects of arterial blood gas tensions on pressor responses to angiotensin II in the pithed rat.

Cited by 5 publications

References 6 publications

Blockade by nifedipine of responses to intravenous bolus injection or infusion of α1‐and α2‐adrenoceptor agonists in the pithed rat

Blockade by nifedipine of responses to intravenous bolus injection or infusion of α1‐and α2‐adrenoceptor agonists in the pithed rat

Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α1‐ and α2‐adrenoceptor agonists in pithed normotensive rats

Physiological Modulation of α-Adrenoceptor and 5HT Receptor Expression in Blood Vessels

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Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

Blockade by nifedipine of responses to intravenous bolus injection or infusion of α₁‐and α₂‐adrenoceptor agonists in the pithed rat

Effects of enalapril on changes in cardiac output and organ vascular resistances induced by α₁‐ and α₂‐adrenoceptor agonists in pithed normotensive rats