Interaction of Nitric Oxide and the Renin Angiotensin System in Renal Hypertensive Rats.

Lee, Byung Ho; Shin, Hwa Sup

doi:10.1254/jjp.74.83

Cited by 6 publications

(1 citation statement)

References 22 publications

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“…The reduction of ACh-induced relaxation in balloon-injured arteries was significantly restored by treatment with SK-1080 (0.3 and 1.0 mg/kg). These results fall in line with previous study indicating that losartan restored the impaired EDRF synthesis/release in balloon-injured carotid arteries in rabbits [20], and our previous data showing that losartan restored ACh-induced aortic relaxation damaged by hypertension in renal hypertensive rats [21]. Interestingly, when SK-1080 (1.0 mg/kg) was administered for 21 days in balloon-injured rats, ACh-induced relaxation of carotid arteries was rather enhanced or greater compared with arteries from normal rats, although without statistical significance.…”

Section: Discussionsupporting

confidence: 93%

Effects of SK-1080 on Intimal Thickening and Impaired Vascular Relaxation after Ballon Injury in Rats

2002

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We investigated the effects of SK-1080, a novel angiotensin AT₁ receptor antagonist, on neointimal proliferation in the rat carotid artery after balloon injury, together with its effects on the impaired endothelium-dependent vascular relaxation. SK-1080 (0.3 and 1.0 mg/kg/day) was orally administered in balloon-injured rats for 21 days (from 6 days before to 14 days after balloon injury). SK-1080 (1 mg/kg) exerted significant effects on three important parameters associated with the intimal thickening induced by balloon injury (50.0% reduction in neointimal area, 42.7% reduction in stenosis ratio and 69.1% increase in lumen/total area ratio). Acetylcholine-induced relaxation was significantly reduced in the balloon-injured carotid arteries (64.0 ± 9.1%), and this impairment of acetylcholine-induced relaxation was significantly restored by SK-1080 (maximal relaxation: 87.1 ± 6.5 and 88.6 ± 1.9% at 0.3 and 1.0 mg/kg, respectively, p < 0.05). However, the endothelial-independent, sodium nitroprusside-induced relaxation was clearly demonstrated and did not differ in carotid arteries from all treatment groups. Furthermore, acetylcholine-induced relaxation was completely inhibited by L-NAME but not by indomethacin. SK-1080 caused a slight hypotension 1 day before balloon injury (8.7%), which gradually returned to the baseline 6 and 13 days after balloon injury. These results suggest that SK-1080 may have therapeutic potential for the treatment of vascular diseases such as restenosis and atherosclerosis.

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Section: Discussionsupporting

confidence: 93%

Effects of SK-1080 on Intimal Thickening and Impaired Vascular Relaxation after Ballon Injury in Rats

2002

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Interaction of nitric oxide and renin angiotensin system in pulmonary arterial circulation of RHR

Lee

Shin

1997

Arch. Pharm. Res.

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We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated pulmonary arterial tension and pulmonary arterial pressure (PAP) in renal hypertensive rats (RHR) made by complete ligation of left renal artery. Losartan induced a depressor response that was smaller in RHR than in normotensive rats (NR) (3.3 and 7.0 mmHg, respectively, at 3.0 mg/kg, p<0.05), and the response was significantly reduced by N(G)-nitro-L-arginine methyl ester (L-NAME). Angiotensin II elevated the PAP (7.6 and 10.8 mmHg at 0.1 mug/kg; 20.3 and 23.6 mmHg at 1.0 mug/kg, respectively) and contracted the isolated pulmonary artery (pD(2): 8.79 and 8.71, respectively) from both NR and RHR with similar magnitude, and these effects were significantly enhanced by L-NAME in NR, but not in HRR. Acetylcholine lowered the PAP slightly less effectively in RHR than in NR (3.8 and 6.0 mmHg at 10 mug/kg, respectively) and relaxed the pulmonary artery precontracted with norepinephrine in both rats with similar magnitude (E(max): 60.8 and 63.6%, respectively), and the effect being completely abolished after pretreatment with L-NAME or removal of endothelial cells. These results suggest that nitric oxide interacts with renin angiotensin system to control the pulmonary vascular tension and pulmonary arterial circulation of RHR.

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Nitric oxide synthase inhibition accelerates the pressor response to low-dose angiotensin II, exacerbates target organ damage, and induces renin escape

Sealey

Chen

et al. 2004

American Journal of Hypertension

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Because nitric oxide may attenuate both the pressor and cytotoxic effects of angiotensin II (Ang II), we investigated whether nitric oxide synthase (NOS) inhibition might accelerate the slow pressor effect of Ang II, and augment target organ damage. Using conscious, chronically catheterized rats, we previously observed that low-dose Ang II (10 ng/kg/min) rapidly increased mean arterial pressure (MAP) by approximately 25 mm Hg. The MAP then remained at this level for 2 to 4 days, and then increased again during the next 5 days by a further 25 mm Hg to a second plateau. In the present study, 7 days of N(omega)-nitro-l-arginine methyl ester (L-NAME; 10 microg/kg/min) alone increased MAP by 16 mm Hg. When Ang II was added to L-NAME, MAP increased as much as with Ang II alone, but then continued to increase until day 4, reaching a plateau as high as that reached only on day 9 of Ang II alone. In approximately half the rats infused with L-NAME + Ang II, plasma renin escaped from Ang II-induced suppression after day 4 of Ang II, and continued to increase for the duration of the study. On the first day that Ang II was added to L-NAME, urinary protein excretion and plasma cardiac troponin T increased, indicating early target organ damage. By the end of the study, all rats treated with L-NAME + Ang II developed tubulointerstitial and glomerular injuries, fibrosis of the renal and cardiac arteries, and cardiac interstitial fibrosis. Target organ damage was greater in rats that developed renin escape than in those in which plasma renin remained suppressed, but was minimal in rats infused with Ang II or L-NAME alone. Taken together, these findings suggest that endogenous NO normally attenuates the pressor response to low-dose Ang II for several days, and protects from Ang II-induced target organ damage. Under conditions of reduced NO bioavailability, which may result from endothelial insufficiency, relatively small changes in circulating Ang II levels may damage target organs. Moreover, renal damage leading to renin escape may initiate a vicious cycle of elevated Ang II production, leading to higher blood pressure and greater target organ damage.

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Interaction of Nitric Oxide and the Renin Angiotensin System in Renal Hypertensive Rats.

Cited by 6 publications

References 22 publications

Effects of SK-1080 on Intimal Thickening and Impaired Vascular Relaxation after Ballon Injury in Rats

Effects of SK-1080 on Intimal Thickening and Impaired Vascular Relaxation after Ballon Injury in Rats

Interaction of nitric oxide and renin angiotensin system in pulmonary arterial circulation of RHR

Nitric oxide synthase inhibition accelerates the pressor response to low-dose angiotensin II, exacerbates target organ damage, and induces renin escape

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