Could the Pharmacological Differences Observed Between Angiotensin II Antagonists and Inhibitors of Angiotensin Converting Enzyme be Clinically Beneficial?

Levens, Nigel; Gasparo, Marc de; Wood, Jeanette M.; Bottari, Serge P.

doi:10.1111/j.1600-0773.1992.tb00977.x

Cited by 22 publications

(11 citation statements)

References 58 publications

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“…However, it cannot be ruled out that the AT 2 receptor is present in vivo, as shown recently in rat aortic tissues by autoradiography 23 or in human renal artery, 17 but either is lost from VSMCs under the in vitro culture conditions or is present in another vascular cell type. Although there is some evidence to suggest that the AT 2 receptor may be involved in growth, 24 our results indicate that the AT, receptor subtype mediates both the hypertrophic and hyperplastic effects of Ang II on VSMCs in culture. Because this receptor subtype also mediates constriction of VSMCs, Ang II may contribute to the development of hypertension via its hypertrophic as well as its vasoconstrictor effects.…”

Section: Discussioncontrasting

confidence: 74%

Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats.

et al. 1992

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This study examines the effects of angiotensin II on hypertrophy and proliferation of aortic smooth muscle cells from spontaneously hypertensive and Wistar-Kyoto rats and the receptor subtypes mediating these effects. In quiescent confluent cells, angiotensin II induced a dose-dependent increase in thymidine and leucine incorporation without stimulating cell proliferation. In nonconfluent cells, angiotensin II stimulated cell proliferation only in combination with a submaximal concentration of fetal caff serum. These effects were enhanced in cells from spontaneously hypertensive rats compared with Wistar-Kyoto rats. The effects of angiotensin II could be blocked by the AT, receptor antagonist DuP 753 but not by the AT 2 receptor ligand PD 123177. In receptor binding studies with cells derived from both rat strains, AT,-typical binding was observed. These data show that the angiotensin II receptors present in vascular smooth muscle cells in culture from both rat strains are of the AT, receptor subtype. This receptor subtype appears to mediate vascular smooth muscle cell hypertrophy and proliferation as well as vasoconstriction. Although no difference in the receptor profile was detectable between the two rat strains, the affinity for the ligands to the receptor and the receptor density tended to be greater in cells from spontaneously hypertensive rats than in cells from Wistar-Kyoto rats. These results may partly explain the greater hypotensive response to angiotensin II receptor blockade in spontaneously hypertensive rats than in Wistar-Kyoto rats, although both rat strains have the same plasma concentrations of angiotensin II. normal or low plasma renin activity and is not considered to be a renin-dependent model of hypertension.1 However, different blockers of the reninangiotensin system, such as renin inhibitors, converting enzyme inhibitors, and nonpeptidic angiotensin II antagonists, lower blood pressure in SHRs after acute and chronic administration.2 -4 Although the renin-angiotensin system is not activated in the circulation in SHRs, it may be at the receptor level or locally in a tissue such as the blood vessel wall.As well as being a potent vasoconstrictor, angiotensin II (Ang II) may also influence the growth of vascular smooth muscle cells (VSMCs). Ang II has been shown to stimulate protein and DNA synthesis in cultured VSMCs 5 -" 7 and, under certain conditions, to induce proliferation of VSMCs and increase extracellular matrix formation. 8 -9 Aortic medial hypertrophy in SHRs is characterized by hypertrophy and poh/ploidy of VSMCs rather than by hyperplasia, and it was shown that this can be normalized by treatment with angiotensin converting enzyme inhibitors.1011 Thus, Ang II may contribute to the development of hypertension in SHRs not Received January 21, 1992; accepted in revised form August 6, 1992. only by its activity as a vasoconstrictor but also by an effect on VSMC growth and vascular hypertrophy. In addition, Ang II may contribute to the proliferative response of VSMCs induced after...

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Section: Discussioncontrasting

confidence: 74%

Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats.

et al. 1992

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“…Losartan reduces proteinuria and glomerular sclerosis in streptozotocin diabetic rats (193) by reversing the permselectivity defect of the filtering membrane in this model. This is similar to findings with ACE inhibitors in diabetic (150,226) and nondiabetic (84.127) patients with renal disease.…”

Section: Nonpeptide Aii-receptor Antagonistssupporting

confidence: 86%

Angiotensin‐II Biochemistry and Physiology: Update on Angiotensin‐II Receptor Blockers

Bermann¹,

Walsh²,

Sowers³

1997

Cardiovascular Drug Reviews

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“…The Ang II AT, receptor antagonists discussed here represent a new class of drugs which appear to have the same indications as the ACE inhibitor but possibly a better tolerability profile' 54 '. Their efficacy in human subjects has been proven in hypertension but has still to be demonstrated for other indications.…”

Section: Resultsmentioning

confidence: 99%

Angiotensin II Receptor Subtypes and Cardiac Function

Gasparo

Rogg

Brink

et al. 1994

European Heart Journal

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Could the Pharmacological Differences Observed Between Angiotensin II Antagonists and Inhibitors of Angiotensin Converting Enzyme be Clinically Beneficial?

Cited by 22 publications

References 58 publications

Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Receptor-mediated effects of angiotensin II on growth of vascular smooth muscle cells from spontaneously hypertensive rats.

Angiotensin‐II Biochemistry and Physiology: Update on Angiotensin‐II Receptor Blockers

Angiotensin II Receptor Subtypes and Cardiac Function

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