scholarly journals Increased superoxide levels in ganglia and sympathoexcitation are involved in sarafotoxin 6c-induced hypertension

2008 ◽  
Vol 295 (5) ◽  
pp. R1546-R1554 ◽  
Author(s):  
Melissa Li ◽  
Xiaoling Dai ◽  
Stephanie Watts ◽  
David Kreulen ◽  
Gregory Fink
Keyword(s):  
Blood Pressure ◽  
Sympathetic Innervation ◽  
Sympathetic Ganglia ◽  
Plasma Norepinephrine ◽  
Sprague Dawley ◽  
Surgical Ablation ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
Hypertension Development

Endothelin (ET) type B receptors (ETBR) are expressed in multiple tissues and perform different functions depending on their location. ETBR mediate endothelium-dependent vasodilation, clearance of circulating ET, and diuretic effects; all of these should produce a fall in arterial blood pressure. However, we recently showed that chronic activation of ETBR in rats with the selective agonist sarafotoxin 6c (S6c) causes sustained hypertension. We have proposed that one mechanism of this effect is constriction of capacitance vessels. The current study was performed to determine whether S6c hypertension is caused by increased generation of reactive oxygen species (ROS) and/or activation of the sympathetic nervous system. The model used was continuous 5-day infusion of S6c into male Sprague-Dawley rats. No changes in superoxide anion levels in arteries and veins were found in hypertensive S6c-treated rats. However, superoxide levels were increased in sympathetic ganglia from S6c-treated rats. In addition, superoxide levels in ganglia increased progressively the longer the animals received S6c. Treatment with the antioxidant tempol impaired S6c-induced hypertension and decreased superoxide levels in ganglia. Acute ganglion blockade lowered blood pressure more in S6c-treated rats than in vehicle-treated rats. Although plasma norepinephrine levels were not increased in S6c hypertension, surgical ablation of the celiac ganglion plexus, which provides most of the sympathetic innervation to the splanchnic organs, significantly attenuated hypertension development. The results suggest that S6c-induced hypertension is partially mediated by sympathoexcitation to the splanchnic organs driven by increased oxidative stress in prevertebral sympathetic ganglia.

Orchidectomy attenuates impaired endothelial effects of a high-salt diet in Sprague–Dawley rats

2011 ◽  
Vol 89 (4) ◽  
pp. 295-304 ◽  
Author(s):  
A.K. Oloyo ◽  
O.A. Sofola ◽  
C.N. Anigbogu
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
High Salt ◽  
Sprague Dawley ◽  
High Salt Diet ◽  
Salt Diet ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

The effect of sex hormones on vascular reactivity is considered one of the underlying factors contributing to gender differences in cardiovascular functions and diseases. Experiments were designed to investigate the role of androgens in salt-induced hypertension by assessing the relaxation response of isolated aortic rings to acetylcholine and sodium nitroprusside in the presence or absence of l-nitroarginine methyl ester in Sprague–Dawley rats. The rats were either orchidectomized or sham-operated, with or without testosterone replacement, and were placed on a normal or high-salt diet for 6 weeks. The results indicate a significant increase (p < 0.001) in the mean arterial blood pressure of rats on the high-salt diet, when compared with control or orchidectomized rats. Orchidectomy elicited a reduction in mean arterial blood pressure (p < 0.01), while testosterone replacement normalized mean arterial blood pressure to values seen in intact rats on the high-salt diet. The high-salt diet reduced the relaxation response to acetylcholine both in the presence and absence of inhibition of endothelial nitric oxide synthase with l-nitroarginine methyl ester. Bilateral orchidectomy attenuated the impaired endothelial function induced by the high-salt diet in rats, but this was reversed by concomitant administration of testosterone, suggesting a role for androgens in enhancing long-term vascular smooth muscle tone and hence maintenance of high blood pressure in salt-induced hypertension.

Sexual dimorphism in angiotensin II-induced hypertension and vascular alterations

2005 ◽  
Vol 83 (5) ◽  
pp. 413-422 ◽  
Author(s):  
R Tatchum-Talom ◽  
K M Eyster ◽  
D S Martin
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
Vascular Function ◽  
Vascular Dysfunction ◽  
Female Rats ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Male And Female Rats ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

Sex differences in the degree of high blood pressure have been described in several forms of experimental animal models of hypertension. However, the influence of sex on angiotensin II-induced hypertension has not been studied. In the present study, we investigated and compared the effects of chronic angiotensin II treatment on blood pressure and vascular function in male and female rats. Chronic treatment with angiotensin II (0.7 mg/kg daily for 10 d) significantly raised arterial blood pressure in male but not female Sprague–Dawley rats; it upregulated the NAD(P)H oxidase gp67 phox subunit in the aorta of male but not female rats; and it exaggerated the vasoconstrictor responses to norepinephrine and serotonin in the mesenteric vascular bed (MVB) of male but not female rats. Vasodilator responses to acetylcholine (ACh) but not papaverine (PPV) or isoprenaline (ISO) were reduced in the MVB of angiotensin II-treated male but not female rats. ACh, but not PPV or ISO dilatory responses were potentiated in the MVB of angiotensin II-treated female rats. The present findings demonstrate that exogenous angiotensin II upregulates aortic NAD(P)H oxidase gp67 phox subunit, and induces hypertension and mesenteric vascular dysfunction only in male rats.Key words: gender, blood pressure, vascular endothelium, angiotensin II hypertension.

Exercise training and its effects with renal hypertensive rats

1985 ◽  
Vol 59 (5) ◽  
pp. 1410-1415 ◽  
Author(s):  
K. D. Marcus ◽  
C. M. Tipton
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Capillary Density ◽  
Heart Weight ◽  
Sprague Dawley ◽  
Vo2 Max ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Resting Blood Pressure ◽  
Renal Hypertensive Rats

The influence of endurance training on functional capacity [maximal O2 consumption (VO2 max)], caudal arterial blood pressure, and myocardial capillary density were investigated in normotensive rats and rats made hypertensive using the two-kidney one-clip approach (Goldblatt's hypertension). Male Sprague-Dawley rats were assigned to sham (N: 120–140 mmHg), moderately hypertensive (MH = 0.30-mm clips, 150–170 mmHg), or severely hypertensive (SH = 0.25-mm clips, 190–230 mmHg) groups. Rats designated to be runners (T) were exercised on a motor-driven treadmill equal to 50–70% of their VO2 max values for 8–12 wk. Compared with their nontrained (NT) controls, training was associated with significantly higher VO2 max values (12–15%) and muscle cytochrome-c oxidase activities (33–78%). Resting systolic blood pressure was not significantly changed in the N-and MH-T subgroups; however, it was 20–30 mmHg higher in the SH-T subgroup. Mean absolute heart weight for only the N-T group was significantly heavier than their NT controls. However, the mean predicted heart weights (heart wt = 0.639 X body wt of N-NT + 0.001 g) of the two SH groups were significantly higher than expected. The SH-T group had a lower (11%) subepicardial capillary density mean than its NT control and significantly fewer capillaries in the subendocardial region than the other five subgroups. It was concluded that moderate exercise training appeared to be detrimental to rats with severe hypertension because it increased resting blood pressure and decreased myocardial capillary density, even though it improved their functioning capacity.

Increased renal α-ENaC and NCC abundance and elevated blood pressure are independent of hyperaldosteronism in vasopressin escape

2006 ◽  
Vol 291 (1) ◽  
pp. F49-F57 ◽  
Author(s):  
Swasti Tiwari ◽  
Randall K. Packer ◽  
Xinqun Hu ◽  
Yoshihisa Sugimura ◽  
Joseph G. Verbalis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Urine Volume ◽  
Sprague Dawley ◽  
Α Subunit ◽  
Water Load ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Solid Diet ◽  
Epithelial Sodium Channel Enac

Previously, we demonstrated that rats undergoing vasopressin escape had increased mean arterial blood pressure (MAP), plasma and urine aldosterone, and increased renal protein abundance of the α-subunit of the epithelial sodium channel (ENaC), the thiazide-sensitive Na-Cl cotransporter (NCC), and the 70-kDa band of γ-ENaC (Song J, Hu X, Khan O, Tian Y, Verbalis JG, and Ecelbarger CA. Am J Physiol Renal Physiol 287: F1076–F1083, 2004; Ecelbarger CA, Knepper MA, and Verbalis JG. J Am Soc Nephrol 12: 207–217, 2001). Here, we determine whether changes in these renal proteins and MAP require elevated aldosterone levels. We performed adrenalectomies (ADX) or sham surgeries on male Sprague-Dawley rats. Corticosterone and aldosterone were replaced to clamp these hormone levels. MAP was monitored by radiotelemetry. Rats were infused with 1-deamino-[8-d-arginine]-vasopressin (dDAVP) via osmotic minipumps (5 ng/h). At day 3 of dDAVP infusion, seven rats in each group were offered a liquid diet [water load (WL)] or continued on a solid diet (SD). Plasma aldosterone and corticosterone and urine aldosterone were increased by WL in sham rats. ADX-WL rats escaped, as assessed by early natriuresis followed by diuresis; however, urine volume and natriuresis were somewhat blunted. WL did not reduce the abundance or activity of 11-β-hydroxsteroid dehydrogenase type 2. Furthermore, the previously observed increase in renal aldosterone-sensitive proteins and escape-associated increased MAP persisted in clamped rats. The densitometry of immunoblots for NCC, α- and γ-70 kDa ENaC, respectively, were (% sham-SD): sham-WL, 159, 278, 233; ADX-SD, 69, 212, 171; ADX-WL, 116, 302, 161. However, clamping corticosteroids blunted the rise at least for NCC and γ-ENaC (70 kDa). Overall, the increase in aldosterone observed in vasopressin escape is not necessary for the increased expression of NCC, α- or γ-ENaC or increased MAP associated with “escape.”

Decreased vascular sensitivity to norepinephrine following exercise training

1981 ◽  
Vol 51 (2) ◽  
pp. 282-287 ◽  
Author(s):  
D. L. Wiegman ◽  
P. D. Harris ◽  
I. G. Joshua ◽  
F. N. Miller
Keyword(s):  
Blood Pressure ◽  
Exercise Training ◽  
Sprague Dawley ◽  
Maximal Increase ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Vascular Sensitivity ◽  
Series Of Experiments ◽  
High Concentrations ◽  
Alpha Chloralose

Twenty Sprague-Dawley rats (230 +/- 9 g; mean +/- SE) were exercised daily for 6 wk by swimming 1 h/day with weights (5% of body wt) attached to their tails. Nineteen additional rats (237 +/- 8 g) remained sedentary in their cages. All animals were anesthetized with urethan (800 mg/kg) and alpha-chloralose (60 mg/kg). In the first series of experiments, increasing doses of norepinephrine were injected into the jugular vein and the responses in mean arterial blood pressure was recorded from a cannulated femoral artery. Exercise training had no effect on the maximal increase in blood pressure, but significantly decreased blood pressure sensitivity to norepinephrine, expressed as a pD2 value (=-log ED 50), from 5.64 +/- 0.07 to 5.20 +/- 0.06. In the second series, the cremaster muscle with intact circulation and innervation was suspended in a tissue bath and norepinephrine in increasing concentrations was added to the cremaster bath. The responses of the main arteriole (approximately 110 micron) and venule (approximately 170 micron) were recorded by television microscopy. Exercise training had no effect on vessel diameters of resting muscle or on the maximal vessel constrictions obtained in response to high concentrations of norepinephrine. Arteriole sensitivity to norepinephrine was significantly decreased (pD2 of 6.69 +/- 0.24 vs. 5.96 +/- 0.18) and there was some tendency for reduced venule sensitivity. These data suggest that exercise training in rats produces a decrease in alpha- or an increase in beta-adrenergic receptor sensitivity.

Ascorbate prevents microvascular dysfunction in the skeletal muscle of the septic rat

2001 ◽  
Vol 90 (3) ◽  
pp. 795-803 ◽  
Author(s):  
John Armour ◽  
Karel Tyml ◽  
Darcy Lidington ◽  
John X. Wilson
Keyword(s):  
Blood Pressure ◽  
Skeletal Muscle ◽  
Cecal Ligation ◽  
Microvascular Dysfunction ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Plasma Ascorbate ◽  
Ascorbate Concentration

Septic patients have low plasma ascorbate concentrations and compromised microvascular perfusion. The purpose of the present experiments was to determine whether ascorbate improves capillary function in volume-resuscitated sepsis. Cecal ligation and perforation (CLP) was performed on male Sprague-Dawley rats. The concentration of ascorbate in plasma and urine, mean arterial blood pressure, and density of continuously perfused capillaries in the extensor digitorum longus muscle were measured 24 h after surgery. CLP caused a 50% decrease (from 56 ± 4 to 29 ± 2 μM) in plasma ascorbate concentration, 1,000% increase (from 46 ± 13 to 450 ± 93 μM) in urine ascorbate concentration, 20% decrease (from 115 ± 2 to 91 ± 2 mmHg) in mean arterial pressure, and 30% decrease (from 24 ± 1 to 17 ± 1 capillaries/mm) in the density of perfused capillaries, compared with time-matched controls. A bolus of intravenous ascorbate (7.6 mg/100 g body wt) administered immediately after the CLP procedure increased plasma ascorbate concentration and restored both blood pressure and density of perfused capillaries to control levels. In vitro experiments showed that ascorbate (100 μM) inhibited replication of bacteria and prevented hydrogen peroxide injury to cultured microvascular endothelial cells. These results indicate that ascorbate is lost in the urine during sepsis and that a bolus of ascorbate can prevent microvascular dysfunction in the skeletal muscle of septic animals. Our study supports the view that ascorbate may be beneficial for patients with septic syndrome.

Physiological Amounts of Angiotensinogen Increase Blood Pressure in Sprague Dawley Rats After I.V. Administration.

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 694-694
Author(s):  
Christoph P R Klett ◽  
Joey P Granger
Keyword(s):  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Transit Time ◽  
Mean Arterial Blood Pressure ◽  
Time Lag ◽  
Plasma Concentrations ◽  
Sprague Dawley ◽  
Angiotensin I ◽  
Arterial Blood ◽  
Sprague Dawley Rats

P9 The synthesis and secretion of hepatic angiotensinogen is controlled by a complex pattern of physiologic and pathophysiologic mediators including glucocorticoids, estrogens, thyroid hormones, cytokines, glucagon,insulin, and prostaglandins. Since plasma concentrations of angiotensinogen are close to the Michaelis Menten constant, it was hypothesized that changes in angiotensinogen plasma concentrations have an influence on the formation rate of angiotensin I and angiotensin II and, therefore, on blood pressure. To further test this hypothesis we injected purified rat angiotensinogen i.v. in Sprague Dawley rats via the femoral vein. Mean arterial blood pressure was measured after arterial cathederization. Control animals had a mean arterial pressure of 131 ± 2 mm Hg before and after the injection of vehicle (saline). The injection of 0.8, 1,2, and 2.9 mg/kg angiotensinogen caused a dose dependend increase in mean arterial blood pressure of 8 ± 0.4, 19.3 ± 2.1, and 32 ± 2.4 mm Hg, respectively. In contrast, the injection of a purified rabbit anti-rat-angiotensinogen antibody 1.4 mg/kg resulted in a significant decrease in blood pressure (-52 ± 3.2 mmHg). In an attempt to analyze how fast and efficient angiotensinogen production can sense regulatory input and convert into adaptation of secretion rate we determined the transit time (time needed for translation and post-translational modifications) for angiotensinogen in a pulse chase experiment employing 35 [S]-methionine as label in freshly isolated hepatocytes. During the chase periode, after quantitative immunoprecipitation, we determined the transit time for angiotensinogen with 2.5 h which is consistent with the constitutive type of angiotensinogen secretion and the time lag found for plasma concentrations to respond to regulatory mediators. In summary we conclude that variations in angiotensinogen plasma concentrations can result in changes in blood pressure. In contrast to renin known as a tonic regulator for the generation of angiotensin I, angiotensinogen seems to be a factor rather important for long-term control of the basal activity of the renin angiotensin system.

Obesity-Induced Hypertension Develops in Young Rats Independently of the Renin-Angiotensin-Aldosterone System

2006 ◽  
Vol 231 (3) ◽  
pp. 282-287 ◽  
Author(s):  
Anita D. Smith ◽  
Michael W. Brands ◽  
Mong-Heng Wang ◽  
Anne M. Dorrance
Keyword(s):  
Blood Pressure ◽  
Blood Glucose ◽  
Vascular Reactivity ◽  
Fasting Blood Glucose ◽  
Plasma Renin ◽  
Diet Group ◽  
Sprague Dawley ◽  
Diet Induced Obesity ◽  
Sprague Dawley Rats ◽  
Induced Hypertension

A correlation exists between obesity and hypertension. In the currently available models of diet-induced obesity, the treatment of rats with a high fat (HF) diet does not begin until adulthood. Our aim was to develop and characterize a model of pre-pubescent obesity-induced hypertension. Male Sprague-Dawley rats were fed a HF diet (35% fat) for 10 weeks, beginning at age 3 weeks. Blood pressure was measured by tail-cuff, and a terminal blood sample was obtained to measure fasting blood glucose, insulin, plasma renin, aldosterone, thiobarbitutic acid reactive substances (TBARS), and free 8-isoprostanes levels. The vascular reactivity in the aorta was assessed using a myograph. Blood pressure was increased in rats fed the HF diet (HF, 161 ± 2 mm Hg vs. control, 137 ± 2 mm Hg, P < 0.05). Blood glucose (HF, 155 ± 4 mg/dL vs. control, 123 ± 5 mg/dL, P < 0.05), insulin (HF, 232 ± 63 pM vs. control, 60 ± 11 pM, P < 0.05), TBARS (expressed as nM of malondialdehyde [MDA]/ml [HF, 1.8 ± 0.37 nM MDA/ml vs. control 1.05 ± 0.09 nM MDA/ml, P < 0.05]), and free 8-isoprostanes (HF, 229 ± 68 pg/ml vs. control, 112 ± 9 pg/ml, P < 0.05) levels were elevated in the HF diet group. Interestingly, plasma renin and aldosterone levels were not different between the groups. The maximum vasoconstriction to phenylephrine (10−4 M) was increased in the HF diet group (HF, 26.1 ± 1.5 mN vs. control 22.3 ± 1.2 mN, P < 0.05). In conclusion, pre-pubescent rats become hypertensive and have increased oxidative stress and enhanced vasoconstriction when fed a HF diet. Surprisingly, this occurs without the increase in renin or aldosterone levels seen in the adult models of diet-induced obesity.

Cardiovascular effects of mycotoxin T-2 after topical application in rats

1987 ◽  
Vol 65 (5) ◽  
pp. 799-802 ◽  
Author(s):  
B. A. Magnuson ◽  
H. B. Schiefer ◽  
D. S. Hancock ◽  
A. R. Bhatti
Keyword(s):  
Blood Pressure ◽  
Histological Examination ◽  
Cardiovascular Effects ◽  
Intraventricular Pressure ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Sprague Dawley Rats ◽  
Negative Effect ◽  
Cardiac Lesions ◽  
Topical Applications

Evidence has been mounting that trichothecenes cause cardiac lesions and cardiovascular effects in general. T-2 toxin, dissolved in dimethyl sulfoxide, was applied in doses of 0, 1.0, 2.0 mg/kg to the skin of Sprague–Dawley rats. Twenty-four hours later, the cardiac function of the animals was assessed, followed by killing and histological examination. It was found that the arterial blood pressure values were lower in the 2.0 mg/kg group, the peak intraventricular pressure was lower in both the 1.0 and 2.0 mg/kg groups, and the resting systolic and diastolic blood pressure values of the 2.0 mg/kg group were lower than the 0 and 1.0 mg/kg groups. The 1.0 and 2.0 mg/kg groups had significantly lower epinephrine-stimulated intraventricular pressure values, indicating reduced contractility. Extended Q–T intervals in electrocardiograms of the 1.0 and 2.0 mg/kg groups suggested also impaired contractility. The histological examination gave equivocal results. It is concluded that topical applications of small doses of T-2 toxin have a noticeable negative effect on cardiovascular function.

scholarly journals Antagonism of orexin receptors in the posterior hypothalamus reduces hypoglossal and cardiorespiratory excitation from the perifornical hypothalamus

2013 ◽  
Vol 114 (1) ◽  
pp. 119-130 ◽  
Author(s):  
Georg M. Stettner ◽  
Leszek Kubin
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Respiratory Rate ◽  
Receptor Antagonist ◽  
Hypoglossal Nerve ◽  
Posterior Hypothalamus ◽  
Sprague Dawley ◽  
Arterial Blood ◽  
Orexin Receptors ◽  
Sprague Dawley Rats

The perifornical (PF) region of the posterior hypothalamus promotes wakefulness and facilitates motor activity. In anesthetized rats, local disinhibition of PF neurons by GABAA receptor antagonists activates orexin (OX) neurons and elicits a systemic response, including increases of hypoglossal nerve activity (XIIa), respiratory rate, heart rate, and blood pressure. The increase of XIIa is mediated to hypoglossal (XII) motoneurons by pathways that do not require noradrenergic or serotonergic projections. We hypothesized that the pathway might include OX-dependent activation locally within the PF region or direct projections of OX neurons to the XII nucleus. Adult, male Sprague-Dawley rats were urethane anesthetized, vagotomized, paralyzed, and ventilated. Gabazine (GABAA receptor antagonist, 0.18 mM, 20 nl) was injected into the PF region, and ∼2 h later, a second gabazine injection was performed preceded by injection of a dual OX1/2 receptor antagonist (almorexant; 90 mM) either into the XII nucleus (40–60 nl at 2–3 rostrocaudal levels; n = 6 rats), or into the PF region (40–60 nl; n = 6 rats). XIIa, respiratory rate, heart rate, and arterial blood pressure were analyzed for 70 min after each gabazine injection. The excitatory effects of PF gabazine on XIIa, respiratory, and heart rates were significantly reduced by up to 44–82% when gabazine injections were preceded by PF almorexant injections, but not when almorexant was injected into the XII nucleus. These data suggest that a significant portion of XII motoneuronal and cardiorespiratory activation evoked by disinhibition of PF neurons is mediated by local OX-dependent mechanisms within the posterior hypothalamus.

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