Effect of captopril on symphathetic neurotransmission in pithed normotensive rats

Dejonge, A; Knape, J. T. A.; Vanmeel, Jca; Kalkman, Ho; Wilffert, Bob; Thoolen, Mjmc; Vanbrummelen, P; Timmermans, P.B.M.W.M.; Vanzwieten, Pa

doi:10.1016/0014-2999(83)90010-9

Cited by 42 publications

(22 citation statements)

References 16 publications

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“…Concern has been expressed that a consequent vasomotor dysfunction may attenuate the response to catecholamines. 17,18 However, a general reduction of vascular tone does not seem to represent a limitation of the present study because an influence of AT 1 receptor blockade on total peripheral resistance had been excluded in the pithed rat model. 19 In addition, the blood pressure-increasing potency of noradrenaline is maintained at basal diastolic blood pressure values considerably lower (ie, 20 mm Hg 10 ) than the minimum values reached in the present study (range 35 to 52 mm Hg).…”

Section: Discussionmentioning

confidence: 92%

Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation

et al. 2004

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Abstract-Blockade of angiotensin II type-1 (AT 1 ) receptors has been shown to reduce the magnitude of the blood pressure response to noradrenaline in pithed rats via an unidentified mechanism. Dose-response curves were established for the noradrenaline-induced (10 Ϫ12 to 10 Ϫ7 mol/kg) increase of diastolic blood pressure in pithed rats treated with tubocurarine, propranolol, and atropine. Candesartan (1 mg/kg) increased the ED 50 of the noradrenaline response (1.3Ϯ0.1 nmol/kg) up to 20-fold. Vasopressor responsiveness to noradrenaline was attenuated specifically, whereas the vasopressin-induced increase in diastolic blood pressure was maintained. Specific involvement of AT 1 receptors was confirmed by equivalent actions of losartan. Blockade of norepinephrine transporter or ␣ 2 -adrenoceptors using desipramine or rauwolscine reduced the losartan-induced shifts in the ED 50 values of noradrenaline by 63% and 21%, respectively. Combined blockade of norepinephrine transporter and ␣ 2 -adrenoceptors eliminated the influence of losartan on noradrenaline sensitivity (ED 50 5.5Ϯ1.3 versus 5.6Ϯ1.2 nmol/kg), a result also observed after sympathetic denervation by reserpine (ED 50 7.1Ϯ0.8 versus 7.8Ϯ0.8 nmol/kg). Our experiments show that the reduction of vascular noradrenaline sensitivity by AT 1 blockade is dependent on the intact functioning of both neuronal noradrenaline uptake via norepinephrine transporter and presynaptic ␣ 2 -mediated autoinhibition, exclusively provided by the sympathetic innervation. These newly identified mechanisms may contribute to the antihypertensive and protective actions of AT 1 blockers. 1 The mechanisms of the various interactions between the renin-angiotensin-aldosterone system and the sympathetic system have been established at different levels and have been shown to bear prominent pathophysiological implications. Angiotensin II (Ang II) stimulates the sympathetic system by activating central nervous tone and catecholamine release 2 and by facilitating the release of catecholamines from peripheral sympathetic neurons via ganglionic 3,4 and axonal presynaptic receptors. 5,6 Ang II has been shown to increase vascular sensitivity to noradrenaline in rats and isolated vessels, 7-9 so that Ang II and noradrenaline exert synergistic actions on vascular tone. As such, it could be proposed that blockade of endogenous Ang II by AT 1 blockers might alter vascular reactivity to exogenous noradrenaline. Indeed AT 1 blockers provoked a reduction in vascular sensitivity to noradrenaline in pithed rats, 6 although discrepant findings were obtained even where similar experimental approaches were pursued. 10 This controversy still requires clarification, particularly as regards the mechanisms by which AT 1 blockers might reduce vascular catecholamine sensitivity.In arterial smooth muscle, Ang II has been shown to potentiate noradrenaline sensitivity by activating protein kinase C and thereby increasing calcium sensitivity. 8 Moreover, short-duration in vivo pretreatment with Ang II also primes the is...

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Section: Discussionmentioning

confidence: 92%

Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation

et al. 2004

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“…Angiotensin II, at subpressor doses, potentiates noradrenaline and nerve stimulation-induced vasoconstriction in the rat (de Jonge et al, 1982;Hatton & Clough, 1982). This may be related to the ability of angiotensin II to modulate noradrenaline release from nerve endings (Zimmerman, 1981) and/or potentiate the postjunctional effects of noradrenaline (Malik & Nasjletti, 1976;Campbell & Jackson, 1979).…”

Section: Discussionmentioning

confidence: 95%

“…This may be related to the ability of angiotensin II to modulate noradrenaline release from nerve endings (Zimmerman, 1981) and/or potentiate the postjunctional effects of noradrenaline (Malik & Nasjletti, 1976;Campbell & Jackson, 1979). Recent studies have used a converting enzyme inhibitor, captopril, to demonstrate the dependency of noradrenaline-induced vasoconstriction on endogenous angiotensin II (de Jonge et al, 1982;Hatton & Clough, 1982). These studies were conducted in pithed rats where converting enzyme inhibition would result in a major decrease in vascular tone.…”

Section: Discussionmentioning

confidence: 99%

Dietary and pharmacological alterations in endogenous angiotensin II: effect on noradrenaline pressor responsiveness in the rat

Jones

Penner

Smyth

1985

British J Pharmacology

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1 Rats were placed on either a low sodium intake (low sodium diet 0.025% dry weight, tap water for drinking) or a high sodium intake (normal sodium diet 0.45% dry weight, 0.9% saline for drinking) for 10 days. The pressor-response curve to angiotensin II in rats previously on a high sodium intake was shifted to the left of that found in rats previously on a low sodium intake. 2 Suppression of endogenous angiotensin II formation with captopril (0.3 mg kg-') or acute volume repletion (3% body wt per 30 min) resulted in a significant parallel shift of the pressor-response curve for angiotensin II to the left in the low salt group. In the high salt group captopril produced a similar but smaller parallel shift of the dose-response curve to the left. 3 Similar manipulation of endogenous angiotensin II concentrations with high and low salt intake plus captopril treatment or acute volume repletion, produced no alterations in the pressor response for noradrenaline. 4 The attenuated in vivo response to angiotensin II in the low salt intake group may be explained in part by the suppressed vascular sensitivity to angiotensin II in this group, as measured in the isolated perfused kidney of the rat. In kidneys from rats previously on a low sodium intake, an enhanced maximal vasoconstrictor response to noradrenaline was observed as compared to kidneys from high sodium intake rats. 5 These results indicate that, whereas alterations in endogenous angiotensin II concentrations within physiological limits affects the response to exogenous angiotensin, there is little if any effect on the pressor response to noradrenaline.

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“…De Jonge et al (21,33) reported that in the pithed NR, captopril reduced basal blood pressure and suppressed the a-adrenoceptor-mediated and ES-induced responses, but the suppression was diminished after the restoration of basal blood pressure by infusion of vasopressin or Ang. II.…”

Section: Effect On the Pressor Response To Es In Bilaterally Nephrec mentioning

confidence: 99%

No Relation of the Suppressive Effect on the Sympathetic Nervous System to the Acute Hypotension Caused by Imidapril and Enalapril

Ogiku

Sumikawa

Ishida

1993

Japanese Journal of Pharmacology

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ABSTRACT-To investigate the involvement of the sympathoinhibitory effect of imidapril and enalapril in their antihypertensive effect at a clinically reasonable dose, we studied whether some responses induced by the stimulation of the sympathetic nervous system (SNS) were affected by intravenous administration of imidaprilat and enalaprilat in curarized pithed spontaneously hypertensive rats. Imidaprilat and enalaprilat (both at 100 pg/kg, i.v.), which are active metabolites of imidapril and enalapril, respectively, suppressed the pressor responses to electrical stimulation (ES) of the spinal cord (T1 L7) and exogenous noradrenaline (NA). The pressor responses to NA were significantly suppressed after either a1 or a2-adrenoceptors were blocked. Furthermore, imidaprilat (100 ,ug/kg, i.v.) suppressed these reduced responses. When the reduced basal blood pressure was restored by vasopressin infusion, imidaprilat and enalaprilat (both at 100 pg/kg, i.v.) did not suppress the responses to ES and exogenous a-adrenoceptor agonists. They affected neither basal plasma concentrations of NA and adrenaline nor ES-induced increase of these catecholamines. These results suggest that the suppressive effects of imidaprilat and enalaprilat on the pressor responses to ES and a-adrenoceptors agonists are apparently observed in pithed SHR because of a reduction of vascular tone and that imidapril and enalapril do not lower the blood pressure through suppressing SNS.

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Effect of captopril on symphathetic neurotransmission in pithed normotensive rats

Cited by 42 publications

References 16 publications

Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation

Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation

Dietary and pharmacological alterations in endogenous angiotensin II: effect on noradrenaline pressor responsiveness in the rat

No Relation of the Suppressive Effect on the Sympathetic Nervous System to the Acute Hypotension Caused by Imidapril and Enalapril

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Effect of captopril on symphathetic neurotransmission in pithed normotensive rats

Cited by 42 publications

References 16 publications

Reduction of Vascular Noradrenaline Sensitivity by AT 1 Antagonists Depends on Functional Sympathetic Innervation

Reduction of Vascular Noradrenaline Sensitivity by AT 1 Antagonists Depends on Functional Sympathetic Innervation

Dietary and pharmacological alterations in endogenous angiotensin II: effect on noradrenaline pressor responsiveness in the rat

No Relation of the Suppressive Effect on the Sympathetic Nervous System to the Acute Hypotension Caused by Imidapril and Enalapril

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Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation

Reduction of Vascular Noradrenaline Sensitivity by AT ₁ Antagonists Depends on Functional Sympathetic Innervation