Hypertension and Impairment of Endothelium-Dependent Relaxation of Arteries from Spontaneously Hypertensive and L-NAME-Treated Wistar Rats.

Abstract

Effects of chronic treatment of normotensive Wistar rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) on blood pressure and on endothelium-dependent relaxation of the aorta, carotid and iliac arteries were studied. The endothelium-dependent relaxation was compared in arteries from normotensive Wistar Kyoto rats (WKY) and genetically hypertensive rats (stroke-prone spontaneously hypertensive rats, SHRSP). Chronic treatment of normotensive Wistar rats with L-NAME caused an elevation of blood pressure. The elevated blood pressure at 15 weeks of age was significantly higher in these animals than that of untreated Wistar rats, but lower than that of SHRSP. Endothelium-dependent relaxation of the arteries induced by acetylcholine (ACh) was almost abolished by chronic treatment with L-NAME. The remaining small relaxation in arteries from L-NAME-treated rats was completely inhibited by application of L-NAME (10(-4) M). In such preparations, higher concentrations of ACh induced a contraction, which was abolished by removal of the endothelium or by an application of indomethacin (10(-5) M). Endothelium-independent relaxation induced by sodium nitroprusside was similar between preparations from untreated and L-NAME-treated Wistar rats. Endothelium-dependent relaxation was significantly impaired in preparations from SHRSP, when compared with that in those from WKY. However, the impairment was less prominent in preparations from SHRSP than in those from L-NAME-treated rats. These results suggest that the impairment of endothelium-dependent relaxation in the arteries from L-NAME-treated rats is not due to the elevated blood pressure resulting from the chronic treatment, and that impairment of NO synthesis by the endothelium does not play a major role in the initiation of hypertension in SHRSP.

Endothelium-Dependent Relaxation in Pulmonary Arteries of L-NAME-Treated Wistar and Stroke-Prone Spontaneously Hypertensive Rats.

“…Chronic administration of L-NAME caused an elevation of blood pressure in Wistar rats as previously reported (Arnal et al, 1992 andBaylis et al, 1992;Ribeiro et al, 1992;Bryant et al, 1995;Küng et al, 1995;Dowell et al, 1996;Takase et al, 1996;Henrion et al, 1997;Ledingham and Laverty, 1997;Moreau et al, 1998;Zhao et al, 1999;Sekiguchi et al, 2001). In the present study, we showed that while chronic treatment of Wistar rats with L-NAME elevated SBP, the pulmonary arterial blood pressure was unchanged.…”

“…L-NAME has been shown to inhibit the synthesis of NO in the endothelium (Rees et al, 1990;Pfeiffer et al, 1996), and such inhibition has been reported to enhance vascular smooth muscle contraction (Martin et al, 1986;Alosachie and Godfraind, 1988;Osugi et al, 1990;Kaneko and Sunano, 1993). We have also observed that EDR of the aorta and of the carotid and iliac arteries from L-NAME-treated rats was impaired (Sekiguchi et al, 2001). This impairment of EDR in arteries of L-NAME-treated rats is thought to be mainly due to inhibition of NO production by the drug (Arnal et al, 1992;Baylis et al, 1992;Ribeiro et al, 1992).…”

“…It has also been reported that endotheliumdependent relaxation (EDR) (Bryant et al, 1995;Küng et al, 1995;Takase et al, 1996;Zhao et al, 1999;Sekiguchi et al, 2001) and cyclic GMP production (Arnal et al, 1992) were decreased by this treatment, indicating some impairment of EDNO production. This may be the cause of hypertension in rats treated with L-NAME chronically.…”

“…Chronic inhibition of NOS by L-NAME has also been reported to induce sustained hypertension in rats (Ribeiro et al, 1992;Bryant et al, 1995;Küng et al, 1995;Dowell et al, 1996;Takase et al, 1996;Henrion et al, 1997;Ledingham and Laverty, 1997;Moreau et al, 1998;Zhao et al, 1999;Sekiguchi et al, 2001). It has also been reported that endotheliumdependent relaxation (EDR) (Bryant et al, 1995;Küng et al, 1995;Takase et al, 1996;Zhao et al, 1999;Sekiguchi et al, 2001) and cyclic GMP production (Arnal et al, 1992) were decreased by this treatment, indicating some impairment of EDNO production.…”

“…This may be the cause of hypertension in rats treated with L-NAME chronically. In these experiments, systemic arteries such as the aorta (Bryant et al, 1995;Zhao et al, 1999), carotid (Sekiguchi et al, 2001), iliac (Sekiguchi et al, 2001) and mesenteric arteries (Dowell et al, 1996;Takase et al, 1996;Zhao et al, 1999) were used to investigate the effects of chronic treatment with L-NAME on EDR. These arteries are thought to be directly affected by increased blood pressure.…”