Central and Peripheral α-Adrenoceptor Number and Responsiveness After Sinoaortic Denervation in the Rabbit

Berthelot, Alain; Hamilton, CA; Ma, Petty; Reid, JL

doi:10.1097/00005344-198207000-00007

Cited by 17 publications

(11 citation statements)

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“…Moreover, in animals that underwent sinoaortic denervation to achieve complete baroreceptor deafferentation, although the bradycardia following phenylephrine injection was abolished, the shift to the left in the phenylephrine dose response curve was small (phenylephrine/dose ratio = 1.7). 12 Thus, we believe that the relatively small decrease in baroreflex sensitivity is unlikely to be a major factor in causing increased phenylephrine pressor response in the hypertensive animals, although a small contribution cannot be excluded.…”

Section: Discussionmentioning

confidence: 91%

“…This pressor response appears to be mediated by direct activation of peripheral postsynaptic a 2 -adrenoceptors on smooth muscle of resistance vessels 7 and has previously been used to examine altered a 2 -adrenoceptormediated pressor responses. 12 Although guanabenz is one of the more specific a 2 -adrenoceptor agonists available, like clonidine it is a partial agonist at the a 2 -adrenoceptor. Individual animals received only one dose of guanabenz in any 24-hour period, as a longlasting central hypotensive effect with a slow offset was observed, which would have interfered with the analysis of the acute peripheral pressor response to the drug.…”

Section: Assessment Of Responses To Alpha-adrenoceptor Agonists and Amentioning

confidence: 99%

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Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Hamilton¹,

Reid²

1983

Hypertension

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SUMMARY Increased pressor responses to norepinephrine and other pressor agents have been reported to occur in human essential hypertension and in several animal models of experimental hypertension. These increased responses might be related to the development of hypertension or could be a secondary consequence of the elevation in blood pressure. We have examined pressor responses to alpha-adrenoceptor agonists and to angiotensin II in male New Zealand White rabbits with perinephritic hypertension. Increased pressor responses were observed for the a, adrenoceptor agonist phenylephrine and the mixed a r /a 2 -adrenoceptor agonist norepinephrine but not for the « 2 adrenoceptor selective agonist guanabenz or angiotensin II. The increase occurred within 7 days of surgery and in some animals was observed when mean arterial pressure was not significantly elevated. It could not readily be attributed to intimal thickening or hypertrophy of the arterial wall, altered basal levels of norepinephrine or epinephrine, changes in norepinephrine clearance, /3-adrenoceptor interactions, or decreased baroreceptor sensitivity. However, the possibility that vascular hypertrophy and decreased baroreflex sensitivity may contribute to the increase at later times cannot be excluded. In all tissues examined, specific prazosin binding was decreased in the older animals and specific clonidine binding was decreased in forebrain. However, these changes were observed In both hypertensive and sham-operated animals and were probably age-related. We believe the increased response to a,-adrenoceptor agonists may be related to changes at a postreceptor site in the coupling of receptor activation to smooth muscle contraction. 1 " 2 Similar observations have been made in animal models of experimental hypertension including spontaneously hypertensive rats 3 and renal hypertensive rabbits. 4 5 Changes in norepinephrine responsiveness may be mediated by /3-receptors, classical postsynaptic a,-adrenoceptors, the presynaptic regulatory a 2 -adrenoceptors, or the recently proposed postsynaptic aj-adrenoceptor 6 ' 7 which may participate in regulation of peripheral resistance. Increased responses to norepinephrine could also be the result of changes in the number of adrenoceptors or their affinity for the neurotransmitter or alternatively secondary to structural changes in the vessel wall. Changes in a-adrenoceptor number have been observed in several brain regions from spontaneously

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Section: Discussionmentioning

confidence: 91%

Section: Assessment Of Responses To Alpha-adrenoceptor Agonists and Amentioning

confidence: 99%

Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Hamilton¹,

Reid²

1983

Hypertension

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“…10 In baroreceptor-intact conscious dogs, vasopressin, administered at slow infusion rates yielding plasma levels of vasopressin of only 30 pg/ml, was shown to induce an increase of blood pressure. 23 " 27 Cowley et al 23 found that the pressor effect of vasopressin was further enhanced following baroreceptor denervation, which decreased the threshold 11-fold and increased the sensitivity to vasopressin up to 100-fold. Therefore, it appears that the DMK-cut, by transecting baroreceptor fibers intracranially, produced concentrations of vasopressin significantly high enough to elevate MAP by 60-70 mm Hg.…”

Section: -*-*•mentioning

confidence: 99%

“…23 -28 N Thus, if sympathetic responses are deficient, vasopressin appears to become a major pressor system, sufficient to elevate and maintain arterial pressure at hypertensive levels. However, in ganglionblocked rats, plasma levels of vasopressin were not higher than those of hypertensive rats with intact sympathetic activity, but the increments of blood pressure in both groups were similar.…”

Section: -*-*•mentioning

confidence: 99%

Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.

Zukowska‐Grojec¹,

Bayorh²,

Zerbe³

et al. 1983

Hypertension

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SUMMARY The role of sympathetic and other pressor systems in the development of fulminant hypertension induced by baroreceptor deafferentation is still unclear. We studied the effects of acute hypertension produced by bilateral dorsomedullary knife cuts lateral to the nucleus tractus solitarii (DMK-cut) on plasma norepinephrine (NE), epinephrine (E), and vasopressin (VP) in conscious, tailartery-cannulated rats. In saline-pretreated (SAL) rats, DMK-cut caused a significant (p < 0.001) rise in mean blood pressure (MAP, +68 ± 3 mm Hg), heart rate (HR, + 97 ± 19 bpm), NE ( + 2.5 ± 0.3 ng/ml), E (+ 2.7 ± 0.4 ng/ml), and VP (+115 ± 34 pg/ml) compared to sham-operated rats. Neither sympathetic blockade with chlorisondamlne (CHLO, 10 mg/kg, s.c.) nor elimination of the pressor effects of VP by use of Brattleboro rats or the VP pressor antagonist resulted in a maximal MAP response significantly different from that in the SAL + DMK-cut group. However, CHLO-pretreatment of Brattleboro rats completely abolished the increase in MAP and HR. It is suggested that the bilateral DMK-cut causes acute hypertension, probably due to the abolition of baroreceptor reflexes by central interruption of neural connections of the nucleus tractus solitarii. It appears that both the increased sympatboadrenomedullary activity and VP release normally contribute to this hypertension; however, either one is sufficient to sustain the elevated blood pressure. (Hypertension 5: 908-915, 1983) KEY WORDS • norepinephrine • epinephrine heart rate • neurogenic hypertension vasopressin • blood pressure O VER the past several years, peripheral or central interruption of baroreceptor reflex pathways has been shown to produce acute hypertension in several different species.1 " 6 In rats, Doba and Reis' have shown that bilateral electrolytic lesions of the nucleus tractus solitarii (NTS) rapidly produce fulminating arterial hypertension. Intense vasoconstriction in specific systemic vascular beds causes a marked increase in total peripheral resistance; this reduces cardiac output and eventually leads to pulmonary edema.7 Similar cardiovascular responses have been produced in rats by dorsolateral medullary knifecut (DMK-cut) lateral to the NTS. 8 A number of mechanisms appear to contribute to this acute and extreme elevation of blood pressure. It has been suggested that hypertension due to NTS lesions is a result of a marked augmentation of sympathetic neuronal discharge, 1 ' 2 4 5 since ganglionic and alpha-adrenergic blockade reverses the pressor re-

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“…1 Recent studies show that this receptor subtype is involved in the maintenance of vascular tone 2 * 3 and the pathophysiology of the hypertensive state. 4 " 7 The vascular response to stimulation of the o^-adrenoceptor depends on its junctional location; postjunctionalry, this receptor mediates vasoconstriction while prejunctionalry, it mediates vasodilation.…”

mentioning

confidence: 99%

Neurogenic histaminergic vasodilation in canine skeletal muscle: mediation by alpha 2-adrenoceptor stimulation.

Camazine

Shannon

Guerrero

et al. 1988

Circulation Research

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This study examines the neurogenic effect of a 2 -adrenoceptor stimulation on skeletal muscle vascular resistance and its relation to the level of background sympathetic activity. The isolated, separately perfused, neurally intact canine gracilis muscle preparation was used since it permits deliberate and quantifiable alterations in background sympathetic activity, as measured by skeletal muscle vascular resistance. Systemic intravenous UK-14304, a highly selective a,-adrenoceptor agonist, produced a precipitous, neurogenic vasodilation that lowered vascular resistance below the subsequently denervated resistance, thus indicating that an active vasodilation was involved. The overall magnitude of the vasodilation was much greater in animals that had been hemorrhaged to elevate background sympathetic activity than in animals that had been transfused to lower background activity. The 4 " 7 The vascular response to stimulation of the o^-adrenoceptor depends on its junctional location; postjunctionalry, this receptor mediates vasoconstriction while prejunctionalry, it mediates vasodilation.8 "" Thus, the net effect of an Oj-adrenoceptor agonist reflects the balance between its postjunctional vasoconstrictor effect and its prejunctional vasodilator effect.Centrally located o^-adrenoceptors, in particular, appear to play a crucial role in the regulation of the cardiovascular system. Stimulation of these receptors inhibits sympathetic neurotransmission and produces a fall in blood pressure.12 As a result, this receptor has been the target of an increasing number of receptorspecific agents to treat hypertension. Clonidine and the more selective c^-adrenoceptor agonists UK-14304 and B-HT 920 are the most potent centrally acting

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Central and Peripheral α-Adrenoceptor Number and Responsiveness After Sinoaortic Denervation in the Rabbit

Cited by 17 publications

References 0 publications

Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Alpha adrenoceptors and autonomic mechanisms in perinephritis hypertension in the rabbit.

Role of catecholamines and vasopressin in cardiovascular responses to bilateral dorsolateral transection of the medulla oblongata in the rat.

Neurogenic histaminergic vasodilation in canine skeletal muscle: mediation by alpha 2-adrenoceptor stimulation.

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