Does a general alteration in nitric oxide synthesis system occur in spontaneously hypertensive rats?

1994 ◽  
Vol 266 (1) ◽  
pp. H272-H278 ◽  
Author(s):  
J. Xiao ◽  
P. K. Pang
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Synthesis System ◽  
Spontaneously Hypertensive ◽  
Proliferation Of Lymphocytes ◽  
General Activation ◽  
Wistar Kyoto ◽  
Synthase Inhibitor

Immune dysfunction has been reported in spontaneously hypertensive rats (SHR). The current study investigated interactions between macrophages or vascular smooth muscle cells (VSMC) and lymphocytes in SHR and examined the role of nitric oxide (NO) in this interaction. SHR macrophages significantly inhibited the proliferation of lymphocytes from SHR and the genetic control, Wistar-Kyoto rats (WKY). This inhibition was reversed by a NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). SHR VSMC also significantly inhibited the proliferation responses of lymphocytes from SHR and WKY. The inhibition was cell density dependent. In addition, L-NMMA fully reversed the inhibition by SHR VSMC. Upon stimulation, the macrophages and VSMC from SHR produced a significantly higher amount of NO compared with those from WKY. These results suggest that the overproduction of NO was involved in the interaction between macrophages or VSMC and lymphocytes in SHR. Increased NO synthase activity in macrophages and VSMC may indicate a general activation of the NO synthesis system in SHR. The alteration of the NO synthesis system may be an important factor contributing to the lymphocyte depression in hypertension.

Contribution of Vascular Nitric Oxide to Basal Blood Pressure in Conscious Spontaneously Hypertensive Rats and Normotensive Wistar Kyoto Rats

1995 ◽  
Vol 89 (2) ◽  
pp. 177-182 ◽  
Author(s):  
Naoyoshi Minami ◽  
Yutaka Imai ◽  
Jun-Ichiro Hashimoto ◽  
Keishi Abe
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Methyl Ester ◽  
Spontaneously Hypertensive Rats ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto Rats ◽  
Basal Blood Pressure ◽  
Wistar Kyoto

1. The aim of this study was to clarify the extent to which vascular nitric oxide contributes to basal blood pressure in conscious spontaneously hypertensive rats and normotensive Wistar Kyoto rats. 2. The contribution of vascular nitric oxide to maintenance of blood pressure was estimated by measuring the pressor response to an intravenous injection of nitric oxide synthase inhibitor, Nω-l-arginine methyl ester, given after serial injections of captopril, vasopressin V1-receptor antagonist (V1-antagonist) and ganglion blocker (pentolinium) in conscious spontaneously hypertensive and Wistar Kyoto rats aged 20–28 weeks. To estimate the ‘amplifier property’ of hypertrophied vasculature in spontaneously hypertensive rats, which is known to modulate pressor responses, the lower blood pressure plateau after serial injections of captopril, V1-antagonist and pentolinium and the maximum blood pressure elicited by subsequent injection of increasing doses of phenylephrine were also measured. 3. The serial injections of captopril, V1-antagonist and pentolinium decreased mean arterial pressure from 164 ± 9 mmHg to 67 ± 2 mmHg and from 117 ± 2 mmHg to 49 ± 1 mmHg in spontaneously hypertensive and Wistar Kyoto rats respectively. The subsequent injection of Nω-l-arginine methyl ester restored mean arterial pressure almost to its control levels in both spontaneously hypertensive and Wistar Kyoto rats. The absolute changes in mean arterial pressure elicited by Nω-l-arginine methyl ester were significantly greater in spontaneously hypertensive than in Wistar Kyoto rats (P < 0.01), but there was no significant difference in the responses to Nω-l-arginine methyl ester when they were expressed as percentages of either the lower blood pressure plateau or maximum blood pressure. 4. These results indicate that basal blood pressure in both spontaneous hypertensive and Wistar Kyoto rats is maintained by a balance between vascular nitric oxide and major pressor systems. They also suggest that the vasodilatory effect of vascular nitric oxide does not differ between spontaneously hypertensive and Wistar Kyoto rats, and that the increased pressor effect of Nω-l-arginine methyl ester in spontaneously hypertensive rats is due to a vascular amplifier mechanism.

Effect of apocynin treatment on renal expression of COX-2, NOS1, and renin in Wistar-Kyoto and spontaneously hypertensive rats

2006 ◽  
Vol 290 (3) ◽  
pp. R694-R700 ◽  
Author(s):  
A. Paliege ◽  
A. Parsumathy ◽  
D. Mizel ◽  
T. Yang ◽  
J. Schnermann ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nadph Oxidase ◽  
Spontaneously Hypertensive Rats ◽  
Plasma Renin ◽  
Juxtaglomerular Apparatus ◽  
Oxidase Inhibitor ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Cox 2 ◽  
Wistar Kyoto

Macula densa (MD) cells of the juxtaglomerular apparatus (JGA) synthesize type 1 nitric oxide synthase (NOS1) and type 2 cyclooxygenase (COX-2). Both nitric oxide (NO) and prostaglandins have been considered to mediate or modulate the control of renin secretion. Reactive oxygen species (ROS) produced locally by NADPH oxidase may influence NO bioavailability. We have tested the hypothesis that in hypertension elevated ROS levels may modify the expression of NOS1 and COX-2 in the JGA, thereby interacting with juxtaglomerular signaling. To this end, spontaneously hypertensive rats (SHR) and Wistar-Kyoto control rats (WKY) received the specific NADPH oxidase inhibitor, apocynin, during 3 wk. Renal functional and histochemical parameters, plasma renin activity (PRA), and as a measure of ROS activity, urinary isoprostane excretion (IP) were evaluated. Compared with WKY, IP levels in untreated SHR were 2.2-fold increased, and NOS1 immunoreactiviy (IR) of JGA 1.5-fold increased, whereas COX-2 IR was reduced to 35%, renin IR to 51%, and PRA to 7%. Apocynin treatment reduced IP levels in SHR to 52%, NOS1 IR to 69%, and renin IR to 62% of untreated SHR, whereas renin mRNA, COX-2 IR, glomerular filtration rate, PRA, and systolic blood pressure remained unchanged. WKY revealed no changes under apocynin treatment. These data show that NADPH oxidase is an important contributor to elevated levels of ROS in hypertension. Upregulation of MD NOS1 in SHR may have the potential of blunting the functional impact of ROS at the level of bioavailable NO. Downregulated COX-2 and renin levels in SHR are apparently unrelated to oxidative stress, since apocynin treatment had no effect on these parameters.

Inhibition of NOS enhances pulmonary vascular changes in stroke-prone spontaneously hypertensive rats

2000 ◽  
Vol 278 (1) ◽  
pp. L81-L89 ◽  
Author(s):  
Rajamma Mathew ◽  
Newton Y.-T. Fan ◽  
Ning Yuan ◽  
Praveen N. Chander ◽  
Michael H. Gewitz ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Pulmonary Arteries ◽  
The Other ◽  
Pulmonary Vasculature ◽  
Vascular Changes ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Medial Wall Thickness

To determine the effects of chronic nitric oxide (NO) blockade on the pulmonary vasculature, 58-day-old spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) and Wistar-Kyoto rats (WKY) received N ω-nitro-l-arginine (l-NNA; 15 mg ⋅ kg−1 ⋅ day−1orally for 8 days). Relaxation to acetylcholine (ACh) in hilar pulmonary arteries (PAs), the ratio of right ventricular (RV) to body weight (RV/BW) to assess RV hypertrophy (RVH), and the percent medial wall thickness (WT) of resistance PAs were examined. l-NNA did not alter the PA relaxation, RV/BW, or WT in WKY. Although the PA relaxation and RV/BW in control SHRSP were comparable to those in WKY, the WT was increased (31 ± 2 vs. 19 ± 1%).l-NNA-treated SHRSP showed two patterns: in one group, the relaxation, RV/BW, and WT were comparable to those in the control SHRSP; in the other, impaired relaxation (36 ± 7 vs. 88 ± 4% for WKY) was associated with an increase in WT (37 ± 1%) and RV/BW (0.76 ± 0.05). Thus the abnormal pulmonary vasculature in SHRSP at <10 wk of age is not accompanied by impaired relaxation in PAs or RVH; however, impaired relaxation is associated with increased WT and RVH.

Exercise training improves aortic endothelium-dependent vasorelaxation and determinants of nitric oxide bioavailability in spontaneously hypertensive rats

2004 ◽  
Vol 96 (6) ◽  
pp. 2088-2096 ◽  
Author(s):  
Drew A. Graham ◽  
James W. E. Rush
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Exercise Training ◽  
Spontaneously Hypertensive Rats ◽  
No Synthase ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Protein Levels ◽  
Endothelial No Synthase ◽  
Endothelium Dependent Relaxation

The present study examined in vitro vasomotor function and expression of enzymes controlling nitric oxide (NO) bioavailability in thoracic aorta of adult male normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) that either remained sedentary (Sed) or performed 6 wk of moderate aerobic exercise training (Ex). Training efficacy was confirmed by elevated maximal activities of both citrate synthase ( P = 0.0024) and β-hydroxyacyl-CoA dehydrogenase ( P = 0.0073) in the white gastrocnemius skeletal muscle of Ex vs. Sed rats. Systolic blood pressure was elevated in SHR vs. WKY ( P < 0.0001) but was not affected by Ex. Despite enhanced endothelium-dependent relaxation to 10-8 M ACh in SHR vs. WKY ( P = 0.0061), maximal endothelium-dependent relaxation to 10-4 M ACh was blunted in Sed SHR (48 ± 12%) vs. Sed WKY (84 ± 6%, P = 0.0067). Maximal endothelium-dependent relaxation to 10-4 M ACh was completely restored in Ex SHR (93 ± 9%) vs. Sed SHR ( P = 0.0011). Nω-nitro-l-arginine abolished endothelium-dependent relaxation in all groups ( P ≤ 0.0001) and caused equal vasocontraction to maximal ACh in Sed SHR and Ex SHR. Endothelium-independent relaxation to sodium nitroprusside was similar in all groups. Protein levels of endothelial NO synthase were higher in SHR vs. WKY ( P = 0.0157) and in Ex vs. Sed ( P = 0.0536). Protein levels of the prooxidant NAD(P)H oxidase subunit, gp91phox, were higher in SHR vs. WKY ( P < 0.0001) and were diminished in Ex vs. Sed ( P = 0.0557). Levels of the antioxidant SOD-1, -2, and catalase enzymes were lower in SHR vs. WKY (all P ≤ 0.0005) but were not altered by Ex. Thus elevated gp91phox-dependent oxidative stress and reduced antioxidant capacity likely contributed to impaired endothelium-dependent vasorelaxation in Sed SHR. Furthermore, reduced gp91phox-dependent oxidative stress and enhanced endothelial NO synthase-derived NO likely contributed to restored endothelium-dependent vasorelaxation in Ex SHR.

Impairment of endothelium-dependent dilatation of basilar artery during chronic hypertension

1990 ◽  
Vol 259 (5) ◽  
pp. H1455-H1462 ◽  
Author(s):  
W. G. Mayhan
Keyword(s):  
Nitric Oxide ◽  
Basilar Artery ◽  
Intravital Microscopy ◽  
Spontaneously Hypertensive Rats ◽  
Chronic Hypertension ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Wistar Kyoto ◽  
Baseline Diameter

The goal of this study was to determine whether responses of the basilar artery are altered during chronic hypertension. We measured the diameter of the basilar artery using intravital microscopy in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Acetylcholine (10 microM) dilated the basilar artery by 25 +/- 4% (means +/- SE) in WKY but by only 2 +/- 2% in SHR. Bradykinin (1.0 microM) dilated the basilar artery by 12 +/- 1% in WKY, but did not alter diameter in SHR (-0.1 +/- 2%). In contrast, nitroglycerin produced similar vasodilatation in WKY and SHR. Next, we examined the possibility that impaired vasodilatation in SHR may be related to the production of a cyclooxygenase constrictor substance. Indomethacin (10 mg/kg iv) did not restore vasodilatation in response to acetylcholine and bradykinin in SHR. Finally, we examined the role of nitric oxide in dilatation of the basilar artery in response to acetylcholine and bradykinin in WKY. NG-Monomethyl-L-arginine (L-NMMA; 1.0 microM) had little effect on baseline diameter but inhibited vasodilation in response to acetylcholine and bradykinin. Vasodilatation in response to nitroglycerin was not altered by L-NMMA. These findings suggest a profound impairment of endothelium-dependent dilatation of the basilar artery during chronic hypertension. In addition, impaired vasodilatation is not related to the production of a cyclooxygenase constrictor substance. Furthermore, dilatation of the basilar artery in WKY in response to acetylcholine and bradykinin appears to be related to the production of nitric oxide or a substance capable of liberating nitric oxide.

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