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Renin-angiotensin blockade improves renal cGMP production via non-AT(2)-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat.
J Renin Angiotensin Aldosterone Syst. 2001 Dec; 2(4):233-9.JR

Abstract

BACKGROUND

To investigate the changes in the angiotensin II (Ang II) receptors and nitric oxide (NO)-cGMP pathway in the rat kidney after nitric oxide synthase (NOS)blockade.

METHODS

Captopril, an angiotensin-converting enzyme (ACE)inhibitor, 20 mg/100 ml; and/or L-158,809 (an Ang II AT1-receptor antagonist, 5 mg/100 ml) and L-NAME (NOS inhibitor, 50 mg/100 ml) were administered orally for 12 weeks. Blood pressure (BP),urinary albumin, urinary cGMP excretion, plasma ANP, and plasma renin activity were measured. In vitro autoradiography was used to locate the Ang II receptors in the kidney.

RESULTS

Captopril and L- 158,809 treatments normalised BP and prevented the appearance of albuminuria in rats receiving L-NAME. Urinary cGMP excretion was significantly increased in L-158,809-treated rats compared with the non-treated group, suggesting that the dysfunctional NO system may be activated by the treatment. AT1-receptor binding in the kidney was inhibited to about 40% of the control value after administration of L- 158,809. The AT2-receptor binding was inhibited to less than 15% of the control value. NOS inhibition had no effect on receptor binding.

CONCLUSION

Blockade of NOS causes hypertension and renal damage. Treatment with an ACE inhibitor and/or Ang II receptor antagonist prevented these changes equally effectively. The stimulatory effect of AT1-receptor antagonism on cGMP production was not mediated by AT2-receptor-dependent mechanisms, since renalAT2-receptor binding density was suppressed following treatment with L-158,809. AT1-receptor blockade per se favours activation of humoral pathways that stimulate cGMP production potentially contributing to renal and vascular protection in hypertension and chronic renal disease.

Authors+Show Affiliations

Minerva Foundation Institute for Medical Research, Biomedicum Helsink, Helsinki, Finland. nina.uhlenius@hel.fNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

11881129

Citation

Uhlenius, N, et al. "Renin-angiotensin Blockade Improves Renal cGMP Production Via non-AT(2)-receptor Mediated Mechanisms in Hypertension-induced By Chronic NOS Inhibition in Rat." Journal of the Renin-angiotensin-aldosterone System : JRAAS, vol. 2, no. 4, 2001, pp. 233-9.
Uhlenius N, Vuolteenaho O, Tikkanen I. Renin-angiotensin blockade improves renal cGMP production via non-AT(2)-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat. J Renin Angiotensin Aldosterone Syst. 2001;2(4):233-9.
Uhlenius, N., Vuolteenaho, O., & Tikkanen, I. (2001). Renin-angiotensin blockade improves renal cGMP production via non-AT(2)-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat. Journal of the Renin-angiotensin-aldosterone System : JRAAS, 2(4), 233-9.
Uhlenius N, Vuolteenaho O, Tikkanen I. Renin-angiotensin Blockade Improves Renal cGMP Production Via non-AT(2)-receptor Mediated Mechanisms in Hypertension-induced By Chronic NOS Inhibition in Rat. J Renin Angiotensin Aldosterone Syst. 2001;2(4):233-9. PubMed PMID: 11881129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Renin-angiotensin blockade improves renal cGMP production via non-AT(2)-receptor mediated mechanisms in hypertension-induced by chronic NOS inhibition in rat. AU - Uhlenius,N, AU - Vuolteenaho,O, AU - Tikkanen,I, PY - 2002/3/7/pubmed PY - 2002/6/6/medline PY - 2002/3/7/entrez SP - 233 EP - 9 JF - Journal of the renin-angiotensin-aldosterone system : JRAAS JO - J Renin Angiotensin Aldosterone Syst VL - 2 IS - 4 N2 - BACKGROUND: To investigate the changes in the angiotensin II (Ang II) receptors and nitric oxide (NO)-cGMP pathway in the rat kidney after nitric oxide synthase (NOS)blockade. METHODS: Captopril, an angiotensin-converting enzyme (ACE)inhibitor, 20 mg/100 ml; and/or L-158,809 (an Ang II AT1-receptor antagonist, 5 mg/100 ml) and L-NAME (NOS inhibitor, 50 mg/100 ml) were administered orally for 12 weeks. Blood pressure (BP),urinary albumin, urinary cGMP excretion, plasma ANP, and plasma renin activity were measured. In vitro autoradiography was used to locate the Ang II receptors in the kidney. RESULTS: Captopril and L- 158,809 treatments normalised BP and prevented the appearance of albuminuria in rats receiving L-NAME. Urinary cGMP excretion was significantly increased in L-158,809-treated rats compared with the non-treated group, suggesting that the dysfunctional NO system may be activated by the treatment. AT1-receptor binding in the kidney was inhibited to about 40% of the control value after administration of L- 158,809. The AT2-receptor binding was inhibited to less than 15% of the control value. NOS inhibition had no effect on receptor binding. CONCLUSION: Blockade of NOS causes hypertension and renal damage. Treatment with an ACE inhibitor and/or Ang II receptor antagonist prevented these changes equally effectively. The stimulatory effect of AT1-receptor antagonism on cGMP production was not mediated by AT2-receptor-dependent mechanisms, since renalAT2-receptor binding density was suppressed following treatment with L-158,809. AT1-receptor blockade per se favours activation of humoral pathways that stimulate cGMP production potentially contributing to renal and vascular protection in hypertension and chronic renal disease. SN - 1470-3203 UR - https://www.unboundmedicine.com/medline/citation/11881129/Renin_angiotensin_blockade_improves_renal_cGMP_production_via_non_AT_2__receptor_mediated_mechanisms_in_hypertension_induced_by_chronic_NOS_inhibition_in_rat_ L2 - http://journals.sagepub.com/doi/full/10.3317/jraas.2001.037?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -