The importance of vasopressin in the development and maintenance of DOC-salt hypertension in the rat.

Crofton, J. T.; Share, Leonard; Shade, Robert E.; Lee-Kwon, W. J.; Manning, Maurice; Sawyer, Wilbur H.

doi:10.1161/01.hyp.1.1.31

Cited by 260 publications

(130 citation statements)

References 18 publications

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“…20 - 22 Similar observations have been made in reduced renal mass hypertension. 19 In the present study, d(CH 2 ) 5 Tyr(Me)-AVP alone had no effect on blood pressure or heart rate in either hypertensive or normotensive rats.…”

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confidence: 69%

“…20 - 21 In addition, vasopressin-deficient Brattleboro rats are also protected against the development of DOC-saline hypertension. 22 " 24 Recent findings in our laboratory have indicated that one-kidney, figure-8 renal wrap hypertension is also a model of sodium-dependent hypertension. This form of hypertension is prevented when rats are maintained on a low sodium intake, while the hypertension is exacerbated when the rats are fed a high sodium diet.…”

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confidence: 99%

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Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension.

1992

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The contribution of the sympathetic nervous system and vasopressin to the maintenance of arterial pressure was investigated in high sodium-fed rats 4 weeks after the induction of one-kidney, figure-8 renal wrap hypertension. Arterial pressure was significantly greater In renal-wrapped rats than in shamoperated animals. The contribution of the sympathetic nervous system was assessed functionally by measuring the arterial pressure response to ganglionic blockade and estimating the apparent rate of release of norepinephrine. The contribution of vasopressin was assessed by administration of the vascular antagonist

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confidence: 69%

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confidence: 99%

Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension.

1992

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“…1 -2 By using some of these antagonists, several investigators were able to demonstrate a pressor role for AVP in normotension, 3 in maintaining blood pressure during hypovolemia, 4 -5 and in certain types of experimental hypertension. 6 Our own earlier studies with the compound d(CH 2 ) 5 -0-(Me)Tyr-AVP, revealed that the pressor function of AVP was most apparent on salt loading, 7 -8 was closely interrelated to those of the RAS and the SNS, and was maximized when the other two were impaired or eliminated. 910 These findings were confirmed and amplified subsequently by other investigators.…”

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Pressor systems in hypertension and congestive heart failure. Role of vasopressin.

Gavras

1990

Hypertension

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Elevated peripheral vascular resistance, which characterizes hypertension and congestive heart failure (the latter regardless of absolute blood pressure level) is maintained to a large extent by the combined effects of three major neurohormonal pressor mechanisms: the renin-angiotensin system, the sympathoadrenal system, and arginine vasopressin. Blockade of one of these mechanisms may lead to compensatory stimulation of the others, thus offsetting in part the hemodynamic benefits of a specific intervention. Combination therapy, designed to attack all three systems (with use of an angiotensin converting enzyme inhibitor, a sympathetic blocker such as clonidine, and an antagonist of the vasopressor action of vasopressin), may help in the treatment of such cases. To illustrate this strategy, two experimental studies, one case of malignant hypertension, and one case of congestive heart failure are presented. (Hypertension 1990;16:587-593) I t is generally recognized that a given level of arterial blood pressure is maintained to a large extent by the combined effects of three major neurohormonal pressor mechanisms: the renin-angiotensin system (RAS), the sympathetic nervous system (SNS), and arginine vasopressin (AVP). Several lines of experimental and clinical work over the years have demonstrated the participation of any one of these pressor mechanisms in the development and maintenance of various types of hypertension-or even in the maintenance of normotension. The first two, the RAS and the SNS, have been extensively investigated, and their research has yielded invaluable new treatments for hypertension and congestive heart failure that have now become part of the routine therapeutic armamentarium. The third, AVP, has long been known as the antidiuretic hormone that regulates fluid homeostasis. Only recently has it become the focus of experimental and clinical investigation as an important vasopressor mechanism with potential relevance in clinical situations characterized by elevated systemic vascular resistance such as hypertension and congestive heart failure. The fact Our own earlier studies with the compound d(CH 2 ) 5 -0-(Me)Tyr-AVP, revealed that the pressor function of AVP was most apparent on salt loading, 7 -8 was closely interrelated to those of the RAS and the SNS, and was maximized when the other two were impaired or eliminated.910 These findings were confirmed and amplified subsequently by other investigators. 1112 Because AVP analogues are known to have species-specific action, we set out to investigate the possible relevance of these findings in human pathophysiology. We took the above mentioned Vi antagonist through the various steps of pharmacological development to obtain an investigational new drug (IND) exemption number from the Food and Drug Administration (FDA) for its use in humans. 13 With this new pharmacological tool, we attempted to clarify the interaction of the three pressor systems-the RAS, the SNS, and AVP-in human hypertension and congestive heart failure. The following two case...

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“…2 A direct vasopressor role for AVP in the maintenance of hypertension in the DOCA-salt hypertension model is suggested by the finding of elevated plasma AVP levels and a fall in BP with intravenous administration of AVP antiserum 3 or VI receptor antagonist. 4 - 5 However, other investigators failed to demonstrate a reduction in BP with acute VI receptor blockade 68 or showed a reduction in BP with acute V2 or acute or chronic V1-V2 receptor antagonism 910 in DOCA-salt hypertension. Thus, the pressor roles of AVP and/or the VI and V2 AVP receptors in both the pathogenesis and maintenance of hypertension in DOCA-salt hypertension in the rat remain unclear.…”

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Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat.

et al. 1994

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We studied the contribution of vasopressin to the maintenance of high blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertension in the rat using the nonpeptide orally effective vasopressin VI receptor antagonist OPC-21268. Binding kinetic studies demonstrated that oral OPC-21268 (30 mg/kg) acted as a competitive antagonist at the vasopressin VI receptor in DOCA-salt and salt control rats. Basal mean intra-arterial blood pressure was 140±4 mmHg (n=12) in DOCA-salt rats compared with 111±2 mm Hg in salt control rats (n=18). Acute oral OPC-21268 (30 mg/kg) significantly (P<.01) reduced mean intra-arterial pressure in DOCA-salt hypertension, with an average maximal decrease of 24±3 mm Hg occurring at 2.5±0.7 hours after dosing. Systolic blood pressure (tail-cuff) in DOCA-salt rats was 178±2 mm Hg. Chronic oral OPC-21268 (30 mg/kg) twice daily for 7 days significantly (P<.01) reduced systolic blood pressure in DOCA-salt hypertension, with an average maximal S everal lines of evidence support a role for arginine vasopressin (AVP) in the development and maintenance of high blood pressure (BP) in the deoxycorticosterone acetate (DOCA)-salt model of hypertension in the rat. Studies in the Brattleboro rat, which is homozygous for hypothalamic diabetes insipidus and unable to synthesize functional AVP, provide indirect evidence for a role of AVP in the pathogenesis of DOCA-salt hypertension. These rats failed to develop hypertension when treated with DOCA and salt unless also treated with exogenous AVP 1 or desamino-D-arginine-8-vasopressin (dDAVP), a V2 agonist with minimal pressor and increased antidiuretic activity.2 A direct vasopressor role for AVP in the maintenance of hypertension in the DOCA-salt hypertension model is suggested by the finding of elevated plasma AVP levels and a fall in BP with intravenous administration of AVP antiserum 3 or VI receptor antagonist. 4-5 However, other investigators failed to demonstrate a reduction in BP with acute VI receptor blockade 68 or showed a reduction in BP with acute V2 or acute or chronic V1-V2 receptor antagonism 910 in DOCA-salt hypertension. Thus, the pressor roles of AVP and/or the VI and V2 AVP receptors in both the pathogenesis and maintenance of hypertension in DOCA-salt hypertension in the rat remain unclear.Received August 9,1993; accepted in revised form February 23, 1994.From the University of Melbourne (Australia), Austin Hospital. Correspondence to Dr Louise M. Burrell, University of Melbourne, Austin Hospital, Studley Rd, Heidelberg 3084, Victoria, Australia. decrease of 27±5 mm Hg. The antihypertensive effect was reversed 5 days after treatment with OPC-21268 was stopped. In water control rats basal systolic pressure (120±l mm Hg, n=20) was unchanged by chronic oral OPC-21268 (30 mg/kg twice daily for 7 days), and this was confirmed by direct measurement of mean intra-arterial pressure. After chronic oral OPC-21268 (30 mg/kg twice daily for 7 days) hepatic VI receptor binding was significantly reduced for up to 10 hours (P<.05). The r...

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The importance of vasopressin in the development and maintenance of DOC-salt hypertension in the rat.

Cited by 260 publications

References 18 publications

Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension.

Sympathetic nervous system in high sodium one-kidney, figure-8 renal hypertension.

Pressor systems in hypertension and congestive heart failure. Role of vasopressin.

Blood pressure-lowering effect of an orally active vasopressin V1 receptor antagonist in mineralocorticoid hypertension in the rat.

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