The Influence of Neonatal Treatment with Guanethidine on the Development of Isolation-Induced Hypertension in Adult Rats

1983 ◽  
Vol 65 (5) ◽  
pp. 469-474 ◽  
Author(s):  
S. M. Gardiner ◽  
T. Bennett

1. Rats housed individually in glass metabolism cages develop hypertension. Since previous experiments have provided some evidence for the involvement of the sympathetic nervous system in the maintenance of the hypertension, the present work was designed to explore the possible involvement of the sympathetic nervous system in the genesis of isolation-induced hypertension. 2. Male and female Wistar rats were treated neonatally with guanethidine, with a protocol designed to produce an extensive peripheral sympathectomy; control rats received saline. 3. The effects of isolation on systolic blood pressure and fluid and electrolyte balances were studied when the rats were mature. 4. Guanethidine-treated rats did not develop hypertension in response to isolation whereas control rats did. 5. There were no significant differences between the fluid and electrolyte balances of the guanethidine-treated rats compared with controls throughout the period of isolation. 6. It is concluded that a fully functional sympathetic nervous system is required for the development of isolation-induced hypertension, but its involvement is not through a modulation of renal function.

2021 ◽  
Vol 22 (10) ◽  
pp. 5388
Author(s):  
Germán Domínguez-Vías ◽  
Ana Belén Segarra ◽  
Manuel Ramírez-Sánchez ◽  
Isabel Prieto

High saturated fat diets have been associated with the development of obesity and hypertension, along with other pathologies related to the metabolic syndrome. In contrast, the Mediterranean diet, characterized by its high content of monounsaturated fatty acids, has been proposed as a dietary factor capable of positively regulating cardiovascular function. These effects have been linked to changes in the local renal renin angiotensin system (RAS) and the activity of the sympathetic nervous system. The main goal of this study was to analyze the role of two dietary fat sources on aminopeptidases activities involved in local kidney RAS. Male Wistar rats (six months old) were fed during 24 weeks with three different diets: the standard diet (S), the standard diet supplemented with virgin olive oil (20%) (VOO), or the standard diet enriched with butter (20%) plus cholesterol (0.1%) (Bch). Kidney samples were separated in medulla and cortex for aminopeptidase activities (AP) assay. Urine samples were collected for routine analysis by chemical tests. Aminopeptidase activities were determined by fluorometric methods in soluble (sol) and membrane-bound (mb) fractions of renal tissue, using arylamide derivatives as substrates. After the experimental period, the systolic blood pressure (SBP) values were similar in standard and VOO animals, and significantly lower than in the Bch group. At the same time, a significant increase in GluAP and IRAP activities were found in renal medulla of Bch animals. However, in VOO group the increase of GluAP activity in renal medulla was lower, while AspAP activity decreased in the renal cortex. Furthermore, the VOO diet also affected other aminopeptidase activities, such as TyrAP and pGluAP, related to the regulation of the sympathetic nervous system and the metabolic rate. These results support the beneficial effect of VOO in the regulation of SBP through changes in local AP activities of the kidney.


2020 ◽  
pp. 405-414
Author(s):  
N DRÁBKOVÁ ◽  
S HOJNÁ ◽  
J ZICHA ◽  
I VANĚČKOVÁ

It is generally accepted that angiotensin II plays an important role in high blood pressure (BP) development in both 2-kidney-1-clip (2K1C) Goldblatt hypertension and in partial nephrectomy (NX) model of chronic kidney disease (CKD). The contribution of sympathetic nervous system and nitric oxide to BP control in these models is less clear. Partial nephrectomy or stenosis of the renal artery was performed in adult (10-week-old) male hypertensive heterozygous Ren-2 transgenic rats (TGR) and normotensive control Hannover Sprague Dawley (HanSD) rats and in Wistar rats. One and four weeks after the surgery, basal blood pressure (BP) and acute BP responses to the consecutive blockade of renin-angiotensin (RAS), sympathetic nervous (SNS), and nitric oxide (NO) systems were determined in conscious rats. Both surgical procedures increased plasma urea, a marker of renal damage; the effect being more pronounced following partial nephrectomy in hypertensive TGR than in normotensive HanSD rats with a substantially smaller effect in Wistar rats after renal artery stenosis. We demonstrated that the renin-angiotensin system does not play so fundamental role in blood pressure maintenance during hypertension development in either CKD model. By contrast, a more important role is exerted by the sympathetic nervous system, the activity of which is increased in hypertensive TGR-NX in the developmental phase of hypertension, while in HanSD-NX or Wistar-2K1C it is postponed to the established phase. The contribution of the vasoconstrictor systems (RAS and SNS) was increased following hypertension induction. The role of NO-dependent vasodilation was unchanged in 5/6 NX HanSD and in 2K1C Wistar rats, while it gradually decreased in 5/6 NX TGR rats.


2013 ◽  
Vol 19 (3) ◽  
pp. 221-226
Author(s):  
N. V. Kuzmenko ◽  
M. G. Pliss ◽  
N. S. Rubanova ◽  
V. A. Tsyrlin

Objective.To examine the mechanisms underlying the activation of the sympathetic nervous system and blood pressure elevation in vasorenal hypertension in the male Wistar rats weighing 250–300 g.Design and methods.We observed the development of renovascular hypertension, beat-to-beat interval and heart rate variability in animals with intact renal nerves and denervated ischemic kidney for 8 weeks after renal artery clamping. Eight weeks later after renal artery clamping in hypertensive rats with denervated ischemic kidney, both-sided renal denervation was performed, and blood pressure was monitored for 6 weeks.Results.Although the ischemic kidney denervation reduces the activity of the sympathetic nervous system, it does not prevent renovascular hypertension development. However, both-sided renal denervation leads to the normalization of blood pressure in the rats with stable renovascular hypertension.Conclusion.We suggest that increased afferent fl ow from structural formations of the ischemic kidney plays an important role for the increased sympathetic nervous system activity.


1979 ◽  
Vol 57 (1) ◽  
pp. 59-64 ◽  
Author(s):  
T. Kubo

Pressor reactivity to a variety of pressor agents after partial ganglionic blockade induced with hexamethonium was investigated in intact, in spinalized, and in chemically sympathectomized, spontaneously hypertensive rats (SHR). Responses of unanaesthetized 6-month-old SHR to noradrenaline, phenylephrine, and angiotensin after hexamethonium administration (32 mg/kg) markedly exceeded those of unanaesthetized, age-matched normotensive Wistar–Kyoto rats (WKR). Responses of anaesthetized SHR to noradrenaline after hexamethonium administration (16 mg/kg) were also increased at the hypertensive stages but not at the prehypertensive stages, when compared with those of anaesthetized normotensive Wistar rats of respective ages. In spinalized and chemically sympathectomized preparations after hexamethonium administration (16 mg/kg), noradrenaline produced equal increases in blood pressure in 6-month-old SHR and WKR. It is suggested that the functional sympathetic nervous system is important for the hyperreactivity of intact SHR.


2007 ◽  
Vol 113 (1) ◽  
pp. 33-40 ◽  
Author(s):  
Niels P. Riksen ◽  
Marlies Bosselaar ◽  
Stephan J.L. Bakker ◽  
Robert J. Heine ◽  
Gerard A. Rongen ◽  
...  

Plasma NEFA (non-esterified fatty acid) concentrations are elevated in patients with obesity. In the present study we first aimed to provide an integral haemodynamic profile of elevated plasma NEFAs by the simultaneous assessment of blood pressure, pulse wave velocity, FBF (forearm blood flow) and sympathetic nervous system activity during acute elevation of NEFAs. Secondly, we hypothesized that NEFA-induced vasodilation is mediated by adenosine receptor stimulation. In a randomized cross-over trial in healthy subjects, Intralipid® was infused for 2 h to elevate plasma NEFAs. Glycerol was administered as the Control infusion. We assessed blood pressure, pulse wave velocity, FBF (using venous occlusion plethysmography) and sympathetic nervous system activity by measurement of noradrenaline and adrenaline. During the last 15 min of Intralipid®/Control infusion, the adenosine receptor antagonist caffeine (90 μg·min−1·dl−1) was administered into the brachial artery of the non-dominant arm. Compared with Control infusion, Intralipid® increased pulse wave velocity, SBP (systolic blood pressure) and pulse pressure, as well as FBF (from 1.8±0.2 to 2.7±0.6 and from 2.3±0.2 to 2.7±0.6 ml·min−1·dl−1 for Intralipid® compared with Control infusion; P<0.05, n=9). Although in a positive control study caffeine attenuated adenosine-induced forearm vasodilation (P<0.01, n=6), caffeine had no effect on Intralipid®-induced vasodilation (P=0.5). In conclusion, elevation of plasma NEFA levels increased pulse wave velocity, SBP and pulse pressure. FBF was also increased, either by baroreflex-mediated inhibition of the sympathetic nervous system or by a direct vasodilating effect of NEFAs. As the adenosine receptor antagonist caffeine could not antagonize the vasodilator response, this response is not mediated by adenosine receptor stimulation.


Hypertension ◽  
1999 ◽  
Vol 34 (1) ◽  
pp. 102-106 ◽  
Author(s):  
Mario J. Carvalho ◽  
Anton H. van den Meiracker ◽  
Frans Boomsma ◽  
Joao Freitas ◽  
Arie J. Man in ‘t Veld ◽  
...  

1992 ◽  
Vol 262 (6) ◽  
pp. E763-E778 ◽  
Author(s):  
I. A. Reid

The renin-angiotensin system plays an important role in the regulation of arterial blood pressure and in the development of some forms of clinical and experimental hypertension. It is an important blood pressure control system in its own right but also interacts extensively with other blood pressure control systems, including the sympathetic nervous system and the baroreceptor reflexes. Angiotensin (ANG) II exerts several actions on the sympathetic nervous system. These include a central action to increase sympathetic outflow, stimulatory effects on sympathetic ganglia and the adrenal medulla, and actions at sympathetic nerve endings that serve to facilitate sympathetic neurotransmission. ANG II also interacts with baroreceptor reflexes. For example, it acts centrally to modulate the baroreflex control of heart rate, and this accounts for its ability to increase blood pressure without causing a reflex bradycardia. The physiological significance of these actions of ANG II is not fully understood. Most evidence indicates that the actions of ANG to enhance sympathetic activity do not contribute significantly to the pressor response to exogenous ANG II. On the other hand, there is considerable evidence that the actions of endogenous ANG II on the sympathetic nervous system enhance the cardiovascular responses elicited by activation of the sympathetic nervous system.


Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Bruno Igreja ◽  
Nuno M Pires ◽  
Lyndon C Wright ◽  
Patrío Soares-da-Silva

The sympathetic nervous system can alter blood pressure by modulation of cardiac output, peripheral vascular resistance and renal function. One strategy for controlling sympathetic nerve function is to reduce the biosynthesis of norepinephrine (NE) via inhibition of dopamine β-hydroxylase (DβH; EC 1.14.17.1 ), the enzyme that catalyses the conversion of dopamine (DA) to NE in sympathetic nerves. BIA 5-1058 is a reversible DβH inhibitor that decreases NE levels in peripheral sympathetically innervated tissues slowing down sympathetic nervous system drive, without effect in brain tissues. In freely moving SHR implanted with radio-telemetry transmitters single administration of BIA 5-1058 showed a dose (3, 30 and 100 mg/Kg) and time dependent effect on blood pressure with no significant effect on heart rate (HR) and total activity monitored over a 96-hour period. The maximum reduction on systolic blood pressure (SBP) was -10.8, -21.1 and -35.2 mmHg for 3, 30 and 100 mg/Kg, respectively and the maximum reduction on diastolic blood pressure (DBP) was -9.9, -18.4 and -24.8 mmHg for 3, 30 and 100 mg/Kg, respectively. The antihypertensive effect of BIA 5-1058 (30 mg/Kg) was further evaluated in combination with efficacious doses of well-known antihypertensive drugs, like the ACE inhibitor captopril, the AT1 receptor antagonist losartan, the diuretic hydrochlorothiazide, beta-blocker metoprolol, the alpha-1 receptor antagonist prazosin, and the calcium channel blocker diltiazem. All drugs were administered orally (single dose) in a cross-over design and the effect was monitored for 72 hours. The combination of BIA 5-1058 with any of the tested antihypertensive drugs caused a stronger and prolonged blood pressure decrease than any of the compounds alone.In conclusion, peripheral DβH inhibitors can be used, alone or in combination with others antihypertensive drugs, to reduce blood pressure.


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