Role of the Pressor Action of Angiotensin IIin Experimental Hypertension

Pals, Donald T.; Masucci, Frederick D.; Denning, George S.; Sipos, Frank; Fessler, Dyral C.

doi:10.1161/01.res.29.6.673

Cited by 294 publications

(117 citation statements)

References 19 publications

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“…To distinguish direct effects of the precursors of A II from those produced by local generation of A II within the vascular tissue, we have investigated the action of these agents on the vasoconstrictor responses to adrenergic stimuli after blockade of the activity of the renin-angiotensin system with either (1) an inhibitor of A I-converting enzyme, SQ 20,881" or (2) a competitive antagonist of A II, [Sar^Ile 8 ]-angiotensin II. 14 The effect of A II and other agents on the vasoconstrictor responses to periarterial nerve stimulation described in this study is presumed to be due to their action on the adrenergic neuromuscular junction, since the work of McGregor 15 and our previous observations 16 indicate that the periarterial nerves to rat mesenteric arteries are postganglionic adrenergic fibers.…”

Section: Facilitation Of Adrenergic Transmission By Locally Generatedmentioning

confidence: 51%

Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.

Malik

Nasjletti

1976

Circulation Research

208

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When studied on isolated rat mesenteric arteries perfused with Tyrode's solution, angiotensin I and angiotensin 11(1 ng/ml), a synthetic tetradecapeptide renin substrate, and a purified hog renin substrate (50-100 ng/ml) potentiated vasoconstrictor responses to sympathetic nerve stimulation and to injected norepinephrine without altering basal pressure. These agents produced a greater augmentation of the vasoconstrictor responses to nerve stimulation than to injected norepinephrine. The potentiation of vasoconstrictor responses to sympathetic nerve stimulation and injected norepinephrine which was elicited by renin substrate and angiotensin I was abolished by an inhibitor of angiotensin I-converting enzyme, SQ 20,881, and by an angiotensin II receptor antagonist, [Sar'-Ile 8 ]angiotensin II. In contrast, the potentiating effect of angiotensin II was blocked only by the latter compound. We conclude that utilization of renin substrate within the vascular wall by renin or renin-like enzymes results in the formation of angiotensin I, which is converted to angiotensin II. Angiotensin in turn potentiates the vasoconstrictor responses to adrenergic stimuli presumably by augmenting release of the adrenergic transmitter and inhibiting its neuronal reuptake as well as by increasing vascular reactivity to norepinephrine. ANGIOTENSIN II (A II), in addition to exerting a potent vasoconstrictor effect, enhances sympathetic activity in several tissues innervated by adrenergic nerves where it augments the response to sympathetic nerve stimulation as well as to injected norepinephrine. 1 Facilitation of adrenergic nervous effects by A II appears to be due to enhanced synthesis 2 and release, 3 ' 5 as well as to inhibition of neuronal reuptake, of norepinephrine. 8 The demonstration of the presence of angiotensin-forming enzymes (renin, angiotensin I-converting enzyme) in extrarenal tissues including blood vessels 7 " 12 raises the possibility that A II formed locally within vascular tissues modulates adrenergic nervous activity. To test this hypothesis we have examined the effect, in rat mesenteric arteries perfused with Tyrode's solution, of natural and synthetic (tetradecapeptide) renin substrates and of both A I and A II on vasoconstrictor responses to periarterial nerve stimulation and to injected norepinephrine. To distinguish direct effects of the precursors of A II from those produced by local generation of A II within the vascular tissue, we have investigated the action of these agents on the vasoconstrictor responses to adrenergic stimuli after blockade of the activity of the renin-angiotensin system with either (1) an inhibitor of A I-converting enzyme, SQ 20,881" or (2) a competitive antagonist of A II, [Sar^Ile 8 ]-angiotensin II. 14 The effect of A II and other agents on the vasoconstrictor responses to periarterial nerve stimulation described in this study is presumed to be due to their action on the adrenergic neuromuscular junction, since the work of McGregor 15 and our previous observations 16 indicate ...

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Section: Facilitation Of Adrenergic Transmission By Locally Generatedmentioning

confidence: 51%

Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.

Malik

Nasjletti

1976

Circulation Research

208

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“…Group 3.-Five of the uninephrectomized rats maintained on 1% NaCl and DOCA which appeared to have reached the malignant phase, as determined by the onset of weight loss and subsequently confirmed by pathologic changes, were selected for infusion with 1-Sar-8-Ala-angiotensin II, a competitive inhibitor of angiotensin II (13). Under ether anesthesia, the femoral vein (PE 10 catheter) and the external iliac artery (PE 20 catheter) were cannulated.…”

Section: Animal Groupsmentioning

confidence: 99%

Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.

Gavras¹,

Brunner²,

Laragh³

et al. 1975

Circulation Research

189

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The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 ± 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 ± 0.02 ng/ml hour" 1 ) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 ± 0.36 ng/ml hour" 1 ) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor l-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 ± 0.01 /^g/g) compared with the control level (0.132 ± 0.02 Mg/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines. KEY WORDS hemoconcentration Wistar ratsangiotensin II inhibitor metabolic balance fibrinoid lesions plasma renin activity• Malignant hypertension has classically been distinguished pathologically from benign essential hypertension by the presence of extensive fibrinoid necrosis of terminal arteries and arterioles as well as proliferative endarteritis. These changes have traditionally been considered to be the consequence of the mechanical stress of excessive filling pressure imposed on the overstimulated arterial muscular wall (1).In human malignant hypertension, aldosterone secretion rates have often been found to be elevated (2). This observation has led to the finding that angiotensin controls aldosterone secretion (3) and to the hypothesis that renin is critically involved in the syndrome of malignant hypertension (4). This thesis has been supported by clinical observations (5) and by animal experiments in

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“…We compared the effects of AngII on p47 phox trafficking with phenylephrine. The latter agent is a peripherally acting alpha1-adrenergic receptor agonist that elevates systemic blood pressure (31), and can affect activity of central cardiovascular pathways involving the NTS (50). When administered over a seven day period, AngII produces an elevation of systemic arterial pressure that is modest, slow, and not sufficient to produce cerebral, cardiac, or renal complications (49).…”

Section: Introductionmentioning

confidence: 99%

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

Glass

Chan

Frys

et al. 2007

Experimental Neurology

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NADPH oxidase-generated superoxide can modulate crucial intracellular signaling cascades in neurons of the nucleus tractus solitarius (NTS), a brain region that plays an important role in cardiovascular processes. Modulation of NTS signaling by superoxide may be linked to the subcellular location of the mobile NADPH oxidase p47 phox subunit, which is known to be present in dendrites of NTS neurons. It is not known, however, if hypertension can produce changes in the trafficking of p47 phox in defined NTS subregions, particularly the preferentially barosensitive dorsomedial NTS (dmNTS), or preferentially gastrointestinal medial NTS (mNTS). We used immunogold electron microscopy to determine if p47 phox localization was differentially affected in dendritic profiles of neurons from these NTS subregions of the rat in response to distinct models of hypertension, namely chronic seven-day subcutaneous administration of angiotensin II (AngII), or phenylephrine. In small (<1 μm) dendritic processes, both AngII and phenylephrine produced a decrease in intracellular p47 phox labeling selectively in dmNTS neurons. In intermediate-size (1-2 μm) dendritic profiles in the dmNTS region only, there was an increase in p47 phox labeling in response to each hypertensive agent, although these changes occurred in different subcellular compartments. There was an increase in non-vesicular labeling in response to AngII, but an increase in surface labeling with phenylephrine. Moreover, each of the changes in p47 phox targeting mentioned above occurred in dendritic profiles with, or without immunoperoxidase labeling for the AngII AT-1A receptor subtype (AT-1A). These results indicate that chronic administration of agents that induce hypertension can also produce changes in the subcellular localization in p47 phox in dmNTS neurons. Thus, systemic hypertension may produce alterations in the trafficking of proteins associated with superoxide production in central autonomic neurons, thus revealing a potentially important neurogenic component of free radical production and systemic blood pressure elevation.

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Role of the Pressor Action of Angiotensin IIin Experimental Hypertension

Cited by 294 publications

References 19 publications

Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.

Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.

Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes.

Changes in the subcellular distribution of NADPH oxidase subunit p47phox in dendrites of rat dorsomedial nucleus tractus solitarius neurons in response to chronic administration of hypertensive agents

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