Antibodies to Renin as Proof of the Pathogenesis of Sustained Renal Hypertension

Wakerlin, G. E.

doi:10.1161/01.cir.17.4.653

Cited by 97 publications

(24 citation statements)

References 2 publications

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“…Several investigators have actively or passively immunized Goldblatt hypertensive rabbits (9, 10), dogs (27,28), or rats (29-31) against angiotensin II or renin. The interpretation of all these results is somewhat difficult because various techniques and hypertensive models have been used, and very often important information such as antibody titers achieved in vitro or in vivo is incomplete.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Brunner¹,

Chang²,

Wallach³

et al. 1972

J. Clin. Invest.

197

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A B S T R A C T During intravenous administration of varying doses of angiotensin II antibody to anesthetized rats, apparently specific vascular receptors were characterized. These receptors compete with administered antibody to bind circulating angiotensin. This competitive phenomenon was used to evaluate the affinity of these receptors for angiotensin. Apparent vascular receptor affinity was defined by the amount of antibody required to block the blood pressure response to exogenous angiotensin. It was found that this receptor affinity varies directly with sodium intake so that the amount of antibody required to block was eightfold greater in normal animals on a high sodium intake, as compared with those on a low sodium intake. Sodium dependence of receptors was also demonstrated in nephrectomized animals, in desoxycorticosterone (DOC)-treated rats, and in chronic renal hypertension. Thus the observed changes in receptor affinity were usually inversely related to measured endogenous angiotensin II levels. Ganglionic blockade increased antibody requirement eightfold. All of these changes were consistent, with no overlap observed in response of individual animals from different groups. These results may explain the variation in pressor activity of angiotensin associated with changes in salt balance and ganglionic blockade.In general, when sufficient antibody was injected to block the effect of exogenous angiotensin a blood pressure lowering effect was also observed. Two exceptions were the nephrectomized and the one-kidney renal hypertensive animals, in both of which antibody administration had no effect on blood pressure.Additional results suggest that changes in receptor affinity are involved in the pathogenesis of various types of experimental hypertensions because the amount of

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Section: Discussionmentioning

confidence: 99%

Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Brunner¹,

Chang²,

Wallach³

et al. 1972

J. Clin. Invest.

197

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“…Proof of principle was established first by use of immunization against renin, 14 followed by studies with a nonspecific inhibitor, pepstatin, and finally with peptide mimics of either prorenin or of the renin substrate angiotensinogen. 15,16 Several of the peptide mimics were developed as possible drugs, and the invaluable knowledge gained has already been well described in the review of renin inhibitors by Staessen et al 17 Parenteral administration of peptide inhibitors to salt-depleted subjects confirmed proof of principle as an effective mechanism of blood pressure reduction, 18 and the development of tetrapeptides led to clinical investigation of orally administered compounds (enalkiren, remikiren, zankiren).…”

Section: The Target For Direct Renin Inhibitionmentioning

confidence: 99%

Aliskiren

Brown

2008

Circulation

119

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Abstract-Aliskiren is the first orally active inhibitor of renin to be approved for clinical use as an antihypertensive agent. The development program has established that at the licensed doses of 150 mg and 300 mg, there are dose-related falls in blood pressure comparable to those seen with other major classes of antihypertensive drugs and that these falls are associated with a placebo level of side effects. Aliskiren was found to be effective either as monotherapy or in combination with drugs from the other major classes. As expected, there was a greater benefit from adding aliskiren to natriuretic drugs than to other blockers of the renin system. However, there was also some consistent benefit from dual renin blockade. Aliskiren is likely to be of most value in patients uncontrolled by, or intolerant of, other classes. Rational understanding of the renin system will maximize its value, for instance, by encouraging greater use of natriuretic agents in patients with resistant hypertension to render their hypertension renin dependent. Whether there are cardiovascular benefits other than blood pressure control in blocking the renin system remains to be demonstrated. It is hoped that long-term outcome studies with aliskiren will finally allow this question to be answered. (Circulation. 2008;118:773-784.)

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“…In studies with anti-renin, passive transfer of dog anti-renin serum produced an antihypertensive effect in the renal hypertensive dog (Wakerlin, 1958). In the rat, dog anti-renin serum inhibited the pressor response to renin, but did not reduce the blood pressure of renal hypertensive rats (Weiser & Hoobler, 1964).…”

Section: Discussionmentioning

confidence: 99%

Effect of rabbit antibodies against angiotensin‐II on the pressor response to angiotensin‐II and renal hypertension in the rat

Hedwall

1968

British J Pharmacology

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1. In the intact or nephrectomized rat, the pressor responses to synthetic angiotensin-II-amide, beta-angiotensin-IL and native " rat angiotensin" could be inhibited by intravenous injection of rabbit serum containing antibodies against synthetic angiotensin-II-amide. 2. The pressor responses to vasopressin or noradrenaline were not influenced by anti-angiotensin serum. 3. A single injection of anti-angiotensin serum inhibited the pressor responses to angiotensin-1I-amide for a period of 2.5 hr. 4. Intravenous infusion or daily intraperitoneal injection of anti-angiotensin serum did not influence blood pressure levels in renal hypertensive rats.

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Antibodies to Renin as Proof of the Pathogenesis of Sustained Renal Hypertension

Cited by 97 publications

References 2 publications

Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Angiotensin II Vascular Receptors: Their Avidity in Relationship to Sodium Balance, the Autonomic Nervous System, and Hypertension

Aliskiren

Effect of rabbit antibodies against angiotensin‐II on the pressor response to angiotensin‐II and renal hypertension in the rat

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