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1.
Renal function of conscious spontaneously hypertensive rats 总被引:2,自引:0,他引:2
Renal clearance studies were performed in conscious 13-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before and during volume expansion by intravenous infusion of isotonic saline. Mean arterial pressure and filtration fraction were greater in SHR, whereas fractional and absolute excretion of sodium and water, glomerular filtration rate, and renal plasma flow in SHR and WKY were not statistically different. This was the case during hydropenia and volume expansion. We did not observe as exaggerated natriuresis after intravenous loading when unanesthetized SHR were compared with the response of WKY. These observations suggest that the kidneys of genetically hypertensive rats of the Okamoto-Aoki strain have adapted to an elevated renal perfusion pressure or that hypertension is required to normalize renal function so that excretion is appropriately matched with intake. 相似文献
2.
The responsiveness of central nervous system alpha 2-adrenergic receptors in the neural control of renal function was compared in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) on normal or high sodium intake (3-4 weeks of 1% NaCl for drinking). The responsiveness of central alpha 2-adrenergic receptors was determined by comparing among groups the dose-response curves for the effects of cumulative intracerebroventricular injections of guanabenz (5, 25, and 125 micrograms) on changes in mean arterial pressure, renal sympathetic nerve activity, and urinary sodium excretion. Guanabenz altered mean arterial pressure similarly in SHR on normal or high sodium intake and in WKY on normal or high sodium intake. High sodium intake shifted the guanabenz-renal sympathetic nerve activity and guanabenz-urinary sodium excretion dose-response curves to the left in SHR and to the right in WKY. The dose-response curves between SHR and WKY on normal sodium intake were similar. Surgical renal denervation or pretreatment with an alpha 2-adrenergic receptor antagonist (rauwolscine, 30 micrograms i.c.v.) attenuated the ability of guanabenz to inhibit renal sympathetic nerve activity or increase urinary sodium excretion in SHR and WKY on either normal or high sodium intake. We conclude that the responsiveness of central nervous system alpha 2-adrenergic receptors regarding the neural control of renal function is increased by high sodium intake in conscious SHR, but not in conscious normotensive WKY. 相似文献
3.
Giuseppe Protasoni Raffaello Golin Simonetta Genovesi Alberto Zanchetti Andrea Stella 《Blood pressure》1996,5(5):305-311
The experiments were performed to study the role of the renal nerves and the reno-renal reflexes in the control of water and sodium excretion in spontaneously hypertensive rats (SHR) compared to their normotensive controls, Wistar Kyoto (WKY) rats. Unilateral renal denervation in anaesthetized animals produced a slight, progressive decrease in arterial pressure in both WKY and SHR rats. The glomerular filtration rate temporarily increased in the kidney that underwent the denervation in the SHR group only. After unilateral renal denervation a sharp increase in water and sodium excretion from the ipsilateral kidney was observed in both WKY and SHR. One hour after the denervation, the percent changes in water and sodium excretion were smaller in WKY (+32 ± 19% and +24 ± 17%) than in SHR rats (+84 ± 15% and +93 ± 20%). In the kidney contralateral to the denervation a reduction in water and sodium excretion was observed and this reduction was prompter in SHR than in WKY rats. One hour after the denervation, the percent changes in water and sodium excretion were similar in WKY (-21 ± 8% and -18 ± 7%) and SHR (-19 ± 6% and -19 ± 7%). In control groups, sham denervation did not cause significant changes in glomerular filtration rate, and urinary water and sodium excretion. Arterial pressure slightly and progressively decreased in both control groups. Electrical stimulation of the efferent renal nerves performed in WKY and SHR produced similar decreases in renal blood flow, glomerular filtration rate, and water and sodium excretion in the two groups for the same frequencies of stimulation. As this finding indicates that renal targets in hypertensive rats are normally responsive to the neural drive, our data demonstrate that renal responses to unilateral renal denervation in hypertensive rats are equal to the responses observed in normotensive rats. Our results indicate that tonically active inhibitory reno-renal reflexes normally operate in spontaneously hypertensive rats. 相似文献
4.
This study, designed in a “blind” fashion, presents, for the first time, a relationship of the histopathology of the kidneys with mean arterial blood pressure (MAP) and age in hypertensive species. Kidneys from 46 spontaneously hypertensive rats (SHR) aged 8–104 weeks were studied using light and electron microscopy (LM and EM, respectively), and their findings were compared with those in age-matched 35 normotensive Wistar rats (NR) and 28 Wistar-Kyoto rats (WKY). A scoring system for the severity of the renal changes (index scores) was developed, and the grading of the renal changes was made without any knowledge of age, MAP, or strain of rat from which kidneys were obtained. The severe (or malignant) renal lesions were found only in old SHR (av: 91 weeks), in contrast to mild or moderate renal lesions (benign) in young SHR (52 weeks or less). The findings of highly significant (P <0.01) correlation between age and index scores along with significant (P <0.05) correlation between MAP and index scores in old SHR indicate that both severity of hypertension and age (i.e., duration of hypertension) in hypertensive species and not severity of hypertension alone are determining factors in the pathogenesis of severe (or malignant) renal lesions. Since old SHR are derivative of the same homogeneous population as young SHR, it appears that the malignant renal lesions observed in old SHR are secondary to prolonged severe hypertension. In contrast, the lack of relationship between index scores of benign lesions (Grades II or III) and MAP or age in young SHR indicates independence of benign renal lesions to hypertension. 相似文献
5.
Yoneda M Sanada H Yatabe J Midorikawa S Hashimoto S Sasaki M Katoh T Watanabe T Andrews PM Jose PA Felder RA 《Hypertension》2005,46(1):58-65
The effect of selectively decreasing renal angiotensin II type 1 (AT1) receptor expression on renal function and blood pressure has not been determined. Therefore, we studied the consequences of selective renal inhibition of AT1 receptor expression in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) in vivo. Vehicle, AT1 receptor antisense oligodeoxynucleotides (AS-ODN), or scrambled oligodeoxynucleotides were infused chronically into the cortex of the remaining kidney of conscious, uninephrectomized WKY and SHR on a 4% NaCl intake. Basal renal cortical membrane AT1 receptor protein was greater in SHR than in WKY. In WKY and SHR, AS-ODN decreased renal but not cardiac AT1 receptors. AT1 receptor AS-ODN treatment increased plasma renin activity to a greater extent in WKY than in SHR. However, plasma angiotensin II and aldosterone were increased by AS-ODN to a similar degree in both rat strains. In SHR, sodium excretion was increased and sodium balance was decreased by AS-ODN but had only a transient ameliorating effect on blood pressure. Urinary protein and glomerular sclerosis were markedly reduced by AS-ODN-treated SHR. In WKY, AS-ODN had no effect on sodium excretion, blood pressure, or renal histology but also modestly decreased proteinuria. The major consequence of decreasing renal AT1 receptor protein in the SHR is a decrease in proteinuria, probably as a result of the amelioration in glomerular pathology but independent of systemic blood pressure and circulating angiotensin II levels. 相似文献
6.
Hertzan-Levy S Skutelsky E Arad T Wollman Y Chernihovsky T Polak-Charcon S Iaina A 《American journal of hypertension》2000,13(7):838-845
Cationic colloidal gold (CCG), a polycationic histochemical probe, was used to analyze the distribution of glomerular basement membrane (GBM) polyanions, mainly heparan sulfate proteoglycan in spontaneous hypertensive rats (SHR) with or without salt loading and antihypertensive treatment with propranolol. The changes of mean GBM width and anionic sites distribution were assessed by electron microscopy. Plasma and urinary nitrates (NO(x)) were measured by nitrite (NO2) + nitrate (NO3), stable metabolites of NO. SHR had decreased NO production and increased GBM width (27%) compared with the control Wistar-Kyoto (WKY) rats. The chronic high dietary salt intake resulted in a significant increase in blood pressure, proteinuria, and renal function in the SHR rats. The chronic high salt dietary intake resulted in a decrease in NO in the WKY and a further reduction in NO production in the SHR. The GBM anionic sites count was similar in the SHR and WKY nonsalt-loaded groups, 13.5 +/- 0.5 and 12.8 +/- 0.4 CCG counts/microm GBM, respectively, but significantly lower in both salt-loaded SHR and WKY, 9.9 +/- 0.55 (P < .01) and 9.6 +/- 0.55 (P < .01) CCG counts/microm GBM, respectively. Antihypertensive treatment with propranolol in the salt-loaded SHR group resulted in lower blood pressure, a further decrease in NO production, but no significant changes in GBM width and anionic sites count. It is concluded that chronic high salt intake may be deleterious to the permselectivity of the GBM. A low NO production state that results from chronic salt loading in already hypertensive rats will result in more severe organ (renal) damage, most probably by the addition of the loss of GBM permselectivity to the existing pathomorphologic changes. 相似文献
7.
The metabolic responses of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) to acute blood loss (30% of the calculated blood volume) have been studied. The initial mean arterial pressure (MAP) was 179 mmHg in SHR and 105 mmHg in WKY. After bleeding, MAP decreased to about 50 mmHg in both groups. SHR failed to increase MAP in the posthemorrhagic period, while in WKY a level of 65-70 mmHg was reached. Metabolic changes in liver and skeletal muscle, indicative of tissue hypoxia, occurred earlier and were more pronounced in SHR than in WKY. In SHR, the ATP content of the liver was almost depleted within 1 h, while during the same time period only a moderate reduction was seen in WKY. Extracellular K+ concentration in sketetal muscle increased more rapidly in SHR than in WKY, but a similar relationship between lactate content and extracellular K+ concentration was found in both groups. The mean posthemorrhagic survival time was only 47 min for SHR, as compared to 193 min for WKY. The present results indicate that a blood loss is more detrimental for hypertensive than normotensive rats. 相似文献
8.
《American journal of hypertension》2001,14(7):722-728
To clarify the function of polymorphonuclear leukocytes (PMN) in spontaneously hypertensive rats (SHR) and the effect of beraprost sodium (BS) on these functions, we examined superoxide anion (O2−) production and adherent activity by PMN, as well as modification of these functions by BS ex vivo and in vitro. In study 1, we measured PMN functions in 4-week-old SHR and Wistar-Kyoto (WKY) rats. In study 2 (ex vivo), 14-week-old SHR received vehicle (n = 6) and BS (30 μg/kg/day [n = 6] and 100 μg/kg/day [n = 7]) once daily for 4 weeks. In study 3 (in vitro), PMN from 18-week-old SHR were incubated with BS (0.1 and 1 μmol/L) and theophylline (200 μmol/L), which is reported to inhibit the PMN O2− production. Systolic blood pressure, platelet counts, and PMN O2− production stimulated by phorbol ester myristate acetate were significantly elevated in 4-week-old SHR compared with WKY (P < .05). Beraprost sodium decreased the ex vivo PMN O2− production, serum superoxide dismutase activity, and platelet counts (P < .05); however, BS did not reduce the in vitro PMN O2− production. These data support our hypothesis that the enhanced PMN function contributes to the cardiovascular damages during the early phase of SHR, and that BS has merit for preventing the O2− related organ damages in this model. 相似文献
9.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(5):455-469
The present study evaluated the activity of jejunal Na+-K+-ATPase and its sensitivity to inhibition by dopamine in spontaneous hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats during low (LS), normal (NS) and high (HS) salt intake. Basal jejunal Na+-K+-ATPase activity in SHR on LS intake was higher than in WKY rats. Jejunal Na+-K+-ATPase activity in WKY rats, but not in SHR, on LS intake was significantly reduced (20% decrease) by dopamine (1 μM) and SKF 38393 (10nM), but not quinerolane (10 nM), this being antagonized the D1 receptor antagonist (SKF 83566). Changing from LS to NS or HS intake in WKY rats increased basal jejunal Na+-K+-ATPase activity and attenuated the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake increased basal jejunal Na+-K+-ATPase activity. Basal renal Na+-K+-ATPase activity in SHR on LS intake was similar to that in WKY rats and was insensitive to inhibition by dopamine . Changing from LS to NS or HS intake in WKY rats increased basal renal Na+-K+-ATPase activity without affecting the inhibitory effect of dopamine. In SHR, changing from LS to NS or HS intake failed to alter basal renal Na+-K+-ATPase activity. It is concluded that inhibition of jejunal Na+-K+ ATPase activity by D1 dopamine receptor activation is dependent on salt intake in WKY rats, and SHR animals fail to respond to dopamine, irrespective of their salt intake. 相似文献
10.
OBJECTIVE: To compare the volumes of renomedullary interstitial cell (RMIC) lipid droplets (putative source of vasodepressor substance) in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats on high and low salt diets as an indication of whether the renomedullary vasodepressor system of the SHR is defective. METHODS: Ten-week-old male SHR and WKY rats received a low (0.05% w/w) or high salt (5.0%) diet for 21 days. Conscious mean arterial pressure (MAP) was measured and the renal papilla perfusion fixed with a high osmolarity fixative. Using electron microscopic stereological techniques, the volume density of lipid in RMIC (VVLipid,RMIC) and the total volumes of lipid (VLipid) and RMIC (VRMIC) in papilla were measured. RESULTS: MAP of SHR (high 155 +/- 3 mmHg; low 151 +/- 3 mmHg) was significantly greater than WKY rats (high 126 +/- 2 mmHg; low 129 +/- 2 mmHg; P< 0.001), however salt diet had no significant effect on MAP. The VLipid of rats on the low salt diet was approximately 2.5 times greater than in rats on the high salt diet (P < 0.01). SHR had significantly greater VLipid than WKY rats irrespective of salt diet (P< 0.05; SHR-low 0.245 +/- 0.031 mm3, SHR-high 0.093 +/- 0.007 mm3; WKY-low 0.126 +/- 0.032 mm3, WKY-high 0.051 +/- 0.020 mm3). Similar differences were seen for VVLipid,RMIC, however VRMIC was not different between rat strains or salt diet groups. CONCLUSIONS: SHR and WKY rats responded similarly to the altered salt diets, and SHR demonstrated greater volumes of stored RMIC lipid droplets irrespective of the level of salt intake. These results indicate that SHR hypertension is not due to a deficiency in the amount of lipid droplets, the putative source of the renomedullary vasodepressor substance and that the renomedullary vasodepressor system of the SHR is capable of responding normally to the physiological stimulus of altered salt intake. 相似文献
11.
To clarify the effect of dietary sodium restriction on the mechanism regulating sodium and water in the development of hypertension, we determined the number of the alpha-adrenoceptors in renal basolateral membrane in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. The rats had been fed a low-sodium (0.5%) or normal-sodium (0.4%) diet from 3 weeks of age. The experiments were performed at 6, 8 and 20 weeks of age in both rat groups. Renal basolateral membranes were prepared using Percoll and radioligand binding studies were performed using 3H-prazosin and 3H-rauwolscine. Systolic blood pressure in SHR was already elevated at 6 weeks of age compared with that in WKY rats and rose to hypertensive levels at 8 weeks of age. The sodium balance in WKY rats on both diets decreased at 8 weeks of age, but that of SHR decreased at 20 weeks of age. The maximum number (Bmax) for the alpha 1-adrenoceptor did not differ in any groups of the WKY rats or SHR. Bmax for the alpha 2-adrenoceptors increased at 8 weeks of age in the low-sodium SHR compared with normal-sodium SHR, but did not increase in WKY rats. The data show that the increases in blood pressure in the SHR occur prior to significant increases in the alpha 2-adrenoceptor density of renal basolateral membrane, and that the modulation of alpha 2-adrenoceptor density in SHR differs from that in WKY rats under sodium restriction. The results suggest that renal alpha 2-adrenoceptors in SHR could relate the regulatory mechanism to sodium reabsorption under sodium restriction rather than to the primary cause of the development of hypertension in SHR. There may be the possibility of an abnormality in renal alpha 2-adrenoceptor mechanism in SHR. 相似文献
12.
The effects of 3 weeks treatment with CGS 10078B (30 mg/kg orally) on systemic and regional haemodynamics and cardiac mass were studied in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. The significant decrease in mean arterial pressure (MAP) (174 +/- 3 versus 156 +/- 4 mmHg, P less than 0.002) in SHR was associated with a significantly slower heart rate. No significant alteration in systemic haemodynamics was observed in WKY rats. The reduced MAP in SHR was related to the preserved blood flow to the vital organs, and therefore reduced renal and cerebrovascular resistances. Left ventricular mass index was reduced in both rat strains of treated animals. Therefore, the reduced MAP and heart rate in the SHR without haemodynamic changes in the WKY indicates that CGS 10078B was an effective antihypertensive agent that decreased cardiac mass in rats through mechanisms that may be dissociated from their haemodynamic effects. 相似文献
13.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(1-2):427-440
Exchangeable sodium, extracellular fluid volume and sodium intake were significantly higher in spontaneously hypertensive rats (SHR) than in normotensive controls. The increased exchangeable sodium was due to the expanded extracellular fluid sodium content.Two kidney one clip Goldblatt renal hypertensive rats develop thirst and high renin levels. When drinking saline the rats have markedly increased exchangeable sodium levels, but those drinking water did not.It is proposed that the exaggerated saline intake leads to a volume dependent component of the hypertension in both models. In the SHR both the salt appetite and the hypertension may be induced by angiotensin acting via central mechanisms. 相似文献
14.
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(4):615-628
It has been demonstrated that endogenous kidney dopamine (DA) contributes to the natriuretic response to acute volume expansion (VE). Several studies suggest that a defect in renal DA-ergic mechanism may play a role in genetic hypertension in humans and rats. The present study was designed to determine the role of renal DA and tubular DA-1 receptors in the natriuretic response to VE in age-matched spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats of 10–12 weeks of age. In pentobarbital-anesthetized rats, VE was carried out by intravenously infusing isotonic sodium chloride (5% body weight) over a period of 60 min. This maneuver evoked pronounced increases in urine output, urinary sodium excretion and urinary DA excretion. However, the natriuretic and diuretic response to VE was significantly reduced in SHR, although the increase in urinary DA excretion was similar in both SHR and WKY rats. During VE no significant changes in glomerular filtration rate or blood pressure were noted in either strain of animals, indicating the involvement of renal tubular mechanisms in the natriuretic response. In a separate group of SHR and WKY rats, pretreatment with DA-1 receptor antagonist SCH 23390 caused significant attenuation of the natriuretic and diuretic response to VE in WKY rats but not in SHR, suggesting that unlike WKY rats kidney DA was not contributing to the natriuretic response to VE in SHR. In another group of animals, the renal effects of exogenously administered DA-1 receptor agonist fenoldopam were examined. Fenoldopam (1 μg/kg/min) produced significant increases in urine output and urinary sodium excretion without causing any alterations in blood pressure or glomerular filtration rate in both SHR and WKY rats. However, the interesting observation was that fenoldopam-induced diuresis and natriuresis were significantly attenuated in SHR compared to the WKY rats. These results show that SHR are not able to eliminate an acute increase in sodium load as efficiently as WKY rats, which may be at least in part due to a defect in renal tubular DA-1 receptor function. 相似文献
15.
Vasorelaxant effects of the chronic treatment with melatonin on mesenteric artery and aorta of spontaneously hypertensive rats 总被引:3,自引:0,他引:3
Girouard H Chulak C Lejossec M Lamontagne D de Champlain J 《Journal of hypertension》2001,19(8):1369-1377
OBJECTIVE: To investigate the effect of a chronic treatment with melatonin on arterial pressure and a possible improvement of the vascular muscarinic and NO synthase (NOS) pathways in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. DESIGN AND METHODS: Mean arterial pressure (MAP), systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) were evaluated in conscious rats treated with 30 mg/kg per day of melatonin during 4 weeks. Changes in MAP were evaluated following an intravenous injection of the NOS inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME). Relaxant effects of acetylcholine (Ach), sodium nitroprusside (SNP), and the calcium ionophore A23187 were examined on mesenteric beds and aortic rings with or without treatment with melatonin. RESULTS: Melatonin produced a significant reduction of MAP, SBP, DBP and HR in SHR (P < 0.05). L-NAME increased the MAP of melatonin-treated SHR by the same magnitude as that of WKY rats which was significantly higher than that of non-treated SHR (P< 0.05). Melatonin treatment improved the maximal relaxation of mesenteric arteries to A23187 in SHR (P < 0.001) to the WKY level and caused a slight increment in Ach- and A23187-induced vasodilations in aorta from SHR and WKY rats (P < 0.05). CONCLUSION: The present study showed that melatonin exerted a bradycardic and an antihypertensive action in SHR. The enhancement by melatonin of the endothelium-dependent vasodilation (Ach and/or A23187) in mesenteric artery and aorta from SHR and WKY rats and the higher increase in MAP following L-NAME treatment in melatonin-treated SHR suggest the contribution of an improved vascular NOS pathway activity in the hypotensive effect of melatonin. 相似文献
16.
DOCA-salt hypertension was produced in 10 male 10-week-old normotensive Wistar-Kyoto (WKY) rats receiving deoxycorticosterone acetate (DOCA; 100 mg/kg, subcutaneous pellet) and 1% NaCl drinking water and was compared with data from 10 age- and sex-matched WKY receiving normal tap water (C). These data were also compared with spontaneously hypertensive (SHR) rats similarly treated. After 10 weeks on these programmes, systemic and regional haemodynamics were determined in conscious rats using microsphere techniques. DOCA-salt treatment increased mean arterial pressure (MAP), total peripheral resistance index (TPRI), cardiac and renal weights in both WKY and SHR. In contrast to SHR (C), the SHR (DOCA) demonstrated more severe MAP elevation (204 +/- 4 versus 185 +/- mmHg; P less than 0.01), more severe systemic and regional (especially renal) vasoconstriction, and malignant vasculitis associated with azotaemia and hyperuricaemia. The hyperuricaemia was related inversely to renal blood flow (r = -0.74; P less than 0.01) and directly to renal vasoconstriction (r = 0.65; P less than 0.05) in SHR (DOCA). These data suggest that in both WKY and SHR, DOCA and salt produced marked cardiovascular changes and SHR rats developed malignant hypertension. 相似文献
17.
Our purpose was to investigate the binding characteristics of central alpha-adrenoceptors during the early stages of the development of hypertension in rats on high and low salt (NaCl) intake. We measured alpha 1-[( 3H]prazosin) and alpha 2-[( 3H]rauwolscine) binding in membranes of the hypothalamus and medulla oblongata of six groups of young Wistar-Kyoto (WKY) rats, spontaneously hypertensive rats (SHR) and subtotally nephrectomized WKY (SN) rats with mean arterial blood pressure (MAP) ranging from normotensive to hypertensive levels after 1 week of salt restriction or loading. In the hypothalamus the SN-high salt rats and both SHR groups had elevated alpha 1-number but there was no change in alpha 2-number. Moreover, MAP was positively correlated with mean hypothalamic alpha 1-number in the six groups. In the medulla oblongata alpha 1-number was unaffected. However, high salt diet influenced medullary alpha 2-binding in the opposite manner in WKY rats versus SN rats and SHR. In these latter groups the affinity was increased and the number decreased in response to high salt intake. Furthermore, a positive correlation between MAP and mean alpha 1:alpha 2 ratio existed in both the hypothalamus and the medulla of the six groups. The data suggest that hypothalamic alpha 1-binding capacity was increased in SHR due principally to a genetic condition which is mimicked by salt loading in the SN rats. Medullary alpha 2-adrenoceptors of WKY, which remained normotensive despite salt loading, responded differently to high salt intake than those of the SN and SHR, whose blood pressure rose significantly.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
18.
《Journal of the American Society of Hypertension》2008,2(2):106-115
Fifty years since thiazide diuretics were introduced, they are established as first-line antihypertensive therapy. Because the thiazide dosing profile lessened, the blood pressure lowering mechanism may lie outside their diuretic properties. We evaluated this mechanism in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) by examining the effects of low-dose hydrochlorothiazide (HCTZ) administration on renin-angiotensin system components. The 7-day, 1.5 mg/kg per day HCTZ did not change systolic pressure (SBP) in WKY, but decreased SBP by 41 ± 2 mm Hg (P < .0001) in SHR, independent of increased water intake, urine output, or alterations in electrolyte excretion. HCTZ significantly increased the plasma concentrations of angiotensin I (Ang I) and angiotensin II (Ang II) in both WKY and SHR while reducing angiotensin-converting enzyme (ACE) activity and the Ang II/Ang I ratio (17.1 ± 2.9 before vs. 10.3 ± 2.9 after, P < .05) only in SHR. HCTZ increased cardiac ACE2 mRNA and activity, and neprilysin mRNA in WKY. Conversely in SHR, ACE2 activity was decreased and aside from a 75% increase in AT1 mRNA in the HCTZ-treated SHR, the other variables remained unaltered. Measures of cardiac mas receptor mRNA showed no changes in response to treatment in both strains, although it was significantly lower in untreated SHR. These data, which document for the first time the effect of low-dose thiazide on the activity of the ACE2/Ang-(1-7)/mas receptor axis, suggest that the opposing arm of the system does not substantially contribute to the antihypertensive effect of thiazides. 相似文献
19.
Central Hypotensive Effects of Nicardipine in Conscious Freely Moving Spontaneously Hypertensive Rat
《Clinical and experimental hypertension (New York, N.Y. : 1993)》2013,35(5):669-676
The central cardiovascular effects of the calcium channel blocker nicardipine was studied in conscious freely moving normotensive Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Nicardipine was administered in a 1.5 μ1 volume into the lateral ventricle of the brain (i.c.v.) or intravenously (i.v.). The injection of vehicle alone did not significantly change mean arterial pressure (MAP) or heart rate (HR). Nicardipine (10,30,100 and 300 μg/kg), intravenously administered, dose-dependently decreased MAP and increased HR in WKY and SHR. However, when administered i.c.v., nicardipine (10 μg/kg) increased MAP and HR in WKY and decreased MAP without any significant change in HR in SHR. These results are consistent with previous work reporting an exaggerated hypotensive response to i.c.v. administration of dihydropyridine calcium channel blockers in anesthetized SHR as compared to WKY. They suggest that a 1,4–dihydropyridine-sensitive pressor system is present in the SHR but not in the WKY. 相似文献
20.
Shokoji T Nishiyama A Fujisawa Y Hitomi H Kiyomoto H Takahashi N Kimura S Kohno M Abe Y 《Hypertension》2003,41(2):266-273
Recent studies have implicated a contribution of oxidative stress to the development of hypertension. Studies were performed to determine the effects of the superoxide dismutase (SOD) mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (Tempol) on vascular superoxide production and renal sympathetic nerve activity (RSNA) in anesthetized Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Compared with WKY rats (n=6), SHR showed a doubled vascular superoxide production, which was normalized by treatment with Tempol (3 mmol/L, n=7). In WKY rats (n=6), Tempol (30 mg/kg IV) significantly decreased mean arterial pressure (MAP) from 108+/-5 to 88+/-6 mm Hg and HR from 304+/-9 to 282+/-6 beats/min. In SHR (n=6), Tempol significantly decreased MAP from 166+/-4 to 123+/-9 mm Hg and HR from 380+/-7 to 329+/-12 beats/min. Furthermore, Tempol significantly decreased RSNA in both WKY rats and SHR. On the basis of group comparisons, the percentage decreases in MAP (-28+/-4%), HR (-16+/-3%) and integrated RSNA (-63+/-6%) in SHR were significantly greater than in WKY rats (-17+/-3%, -9+/-2%, and -30+/-4%, respectively). In SHR, changes in integrated RSNA were highly correlated with changes in MAP (r=0.85, P<0.0001) during administration of Tempol (3, 10, and 30 mg/kg IV). In both WKY rats and SHR (n=4, respectively), intracerebroventricular injection of Tempol (300 micro g/1 micro L) did not alter MAP, HR, or RSNA. Intravenous administration of a SOD inhibitor, diethyldithio-carbamic acid (30 mg/kg), significantly increased MAP, HR, and integrated RSNA in both WKY rats and SHR (n=6, respectively). These results suggest that augmented superoxide production contributes to the development of hypertension through activation of the sympathetic nervous system. 相似文献