Development of Hypertension and Life Span in Stroke-Prone Spontaneously Hypertensive Rats During Oral Long-Term Treatment with Various Antihypertensive Drugs

Gries, J; Kretzschmar, R; Neumann, Barbara

doi:10.1097/00005344-198900134-00024

Cited by 19 publications

(14 citation statements)

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“…The amount of chloride provided as KCl in the current study has been shown to increase significantly plasma levels of chloride in the SHRSP 11, 13. Hydrochlorothiazide, 25 mg per kg BW per day, was shown to attenuate the increase in blood pressure and to extend life span in the SHRSP 14. Increasing the dose to 50 mg per kg BW per day did not amplify either effect 14.…”

Section: Methodsmentioning

confidence: 51%

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Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis

Schmidlin

Tanaka²,

Sebastián³

et al. 2010

Journal of Hypertension

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Objective-To test the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the pressor effect of selective dietary chloride loading depends on a positive external sodium balance.Methods-In 43 male SHRSP fed a Japanese style diet containing a low normal amount of NaCl (0.4%) we compared the effects on telemetrically measured systolic blood pressure (SBP) of hydrochlorothiazide, 25 mg/kg per day, alone ("TZ", n=11); hydrochlorothiazide combined with either KCl ("KCLTZ", 2%K, n=10) or KHCO 3 ("KBCTZ", 2%K, n=11) and no hydrochlorothiazide ("CTL", n=11) over a 10-week period starting at 10 weeks of age.Results-With either TZ or KBCTZ, SBP did not increase above baseline values. However, KCLTZ induced a sustained increase in SBP of 17 mmHg (p<0.0001), an increase almost half that occurring without hydrochlorothiazide (CTL), 38 mmHg (p<0.0001). Such divergence of blood pressures with KCLTZ and KBCTZ began over the first three days of their administration, even while they induced similarly negative external sodium balances, a positive one occurring only in CTL. Body weight increased more without, than with, hydrochlorothiazide, but did not differ between KCLTZ and KBCTZ. Changes in SBP occurring on the 2 nd day after treatment assignment predicted final changes.Conclusions-These results demonstrate that in the SHRSP, dietary KCl loading can induce a pressor effect despite concomitant hydrochlorothiazide-induced natriuresis that elicits a negative external sodium balance. The results provide evidence that in the SHRSP the pressor effect of selective chloride loading does not depend on a positive external sodium balance, but rather on a mechanism actuated by chloride per se.

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Section: Methodsmentioning

confidence: 51%

“…Hydrochlorothiazide, 25 mg per kg BW per day, was shown to attenuate the increase in blood pressure and to extend life span in the SHRSP 14. Increasing the dose to 50 mg per kg BW per day did not amplify either effect 14. Deionized drinking water was supplied ad libitum.…”

Section: Methodsmentioning

confidence: 99%

Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis

Schmidlin

Tanaka²,

Sebastián³

et al. 2010

Journal of Hypertension

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“…ACE inhibition 15,21 and dietary potassium administration, 22 with no or only a small reduction in blood pressure, substantially prolonged survival in salt-loaded SHRSP. In contrast, a thromboxane A 2 synthase inhibitor, 23 hydralazine, and diuretics, 24 which all reduced blood pressure, did not prevent cerebral edema or significantly prolong survival.…”

Section: Early Therapymentioning

confidence: 86%

Early-Onset But Not Late-Onset Endothelin-A–Receptor Blockade Can Modulate Hypertension, Cerebral Edema, and Proteinuria in Stroke-Prone Hypertensive Rats

et al. 1999

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Abstract-The ability of endothelin receptor blockade to prevent and to treat established cerebral and renal injury was explored in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP) with the endothelin receptor subtype-A antagonist A127722. SHRSP were subjected to 1% NaCl intake. The start of treatment with A127722 (35 and 70 mg ⅐ kg, respectively) was either synchronized with salt loading or initiated after the first observation of cerebral edema with T 2 -weighted magnetic resonance imaging. In untreated control animals median survival was 54 days (range, 32 to 80 days) after the start of salt loading. Early-onset A127722 treatment increased median survival to 233 days (range, 92 to 407 days; PϽ0.05 versus controls) with 35 mg/kg and to 124 days (range, 97 to 169 days; PϽ0.05 versus control) with 70 mg/kg. The development of cerebral edema was prevented, and systolic blood pressure and proteinuria were dose-dependently reduced. However, all rats in the 70-mg/kg treatment group developed hemorrhages in the basal ganglia shortly before death. Late-onset A127722 treatment failed to affect survival, systolic blood pressure, or proteinuria. Nevertheless, cerebral edema was reduced but not as well as in early-onset treatment. Development of hypertension, cerebral edema, and proteinuria was prevented in SHRSP when A127722 treatment was initiated at the start of salt-loading. However, A127722 treatment did not prolong survival in SHRSP with cerebral edema. This suggests that in SHRSP the endothelin A receptor participates actively in the development of increased blood pressure and initiation of organ damage but participates minimally in established malignant hypertension and progression of target-organ damage. (Hypertension. 1999;33:137-144.) Key Words: edema, cerebral Ⅲ rats, inbred strains Ⅲ magnetic resonance imaging Ⅲ endothelin Ⅲ receptors, endothelin Ⅲ proteinuria R ecently, endothelin (ET) receptor blockers have been advanced as possible antihypertensive drugs. 1 It has been suggested that ET blockers may be particularly beneficial in modulating target-organ damage because of their antiproliferative actions. 2 The predominant ET receptor expressed in vascular smooth muscle cells is the ET A subtype that is mainly responsible for the vasoconstrictor 3 and mitogenic 4 effects of ET-1. ET receptor blockade has proven to be effective in ameliorating the development of hypertension and renal damage in chronic rat models, including renal failure, 5 nitric oxide synthase inhibition, 6 deoxycorticosterone acetate-salt treatment, 7 deoxycorticosterone acetatesalt-treated spontaneously hypertensive rat (SHR), 8 and in stroke-prone SHR (SHRSP) with or without salt treatment, 9 but therapeutic effects on manifest target-organ damage, such as cerebral edema and renal injury, have not yet been reported.To explore the role of ET-1 in severe hypertension and related target-organ damage, we used the salt-loaded SHRSP, 10 a model in which we found consecutive development of hypertension, proteinuria, and cerebral e...

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“…In some (Anderson et al 1986) but not all studies (Griffin et al 1994), angiotensin-converting enzyme inhibitors have shown superior renoprotective properties compared with other antihypertensive drugs, and this has been linked to the ability of these drugs to reduce glomerular hypertension independently of the systemic blood pressure (Meyer et al 1987).…”

mentioning

confidence: 99%

Effects of Perindopril and Hydrochlorothiazide on the Long‐Term Progression of Lithium‐Induced Chronic Renal Failure in Rats

Christensen

Shalmi

Hansen

et al. 1997

Pharmacology & Toxicology

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Administration of lithium in the diet to new-born rats induces chronic renal failure associated with hypertension, proteinuria and irreversible tubulo-interstitial morphological changes. In the present study we induced chronic renal failure by administration of lithium for 16 weeks to new-born rats, and examined the spontaneous course of this nephropathy and the effects of antihypertensive treatment with either perindopril (12 mg/kg diet) or hydrochlorothiazide (50C 1000 mg/kg diet) during a 24 weeks follow up period without lithium. In the placebo group, progression to terminal uraemia occurred in all rats with severe renal failure (initial P, , , >15 mM) (10 of 18). Rats with mild-moderate renal failure (P,,, 9-1 5 mM) showed no deterioration in renal function despite persistent systolic hypertension and irreversible structural renal changes. Perindopril normalized the blood pressure in all rats but did not prevent the progression to terminal uraemia (8 of 18). Hydrochlorothiazide partially controlled the hypertension and accellerated the progression of uraemia without increasing the mortality (7 of 17). Irrespective of treatments, the predominant quantitative structural changes (e.g. decreased volume of proximal tubular cells) showed significant correlations with the degree of renal dysfunction, but not with systolic blood pressure in the surviving rats. It is concluded that progression of lithium-induced nephropathy to terminal uraemia occurs when the nephrotoxic insult results in a more than 50% reduction of the glomerular filtration rate, judged from P, , , levels. The failure of effective antihypertensive treatment with an angiotensin-converting enzyme inhibitor to modify the progression suggests that in this model, systemic or glomerular hypertension may not be an important pathophysiological factor. The structural and functional deterioration observed in Li-uraemic rats during treatment with hydrochlorothiazide remains unexplained.The authors have developed a unique model of chronic renal failure by administration of lithium in the diet to newborn Wistar rats for 8-16 weeks (Christensen et al. 1990). When given lithium in the early postnatal period, but not in the prenatal period (Christensen et al. 1982), rats develop uraemia associated with proteinuria and arterial hypertension (Christensen et al. 1992). The primary target for Liinduced nephrotoxicity seems to be the distal part of the nephron (Darrup et al. 1988), but in the advanced state lithium-induced chronic renal failure is characterized by interstitial nephropathy with loss of proximal tubular mass, cortical microcysts, focal interstitial fibrosis and glomerular heterogeneity . Li nephropathy in rats has several characteristics in commen with human tubulo-interstitial diseases (Marcussen 1992;Bohle et al. 1987) in that both types of nephropathies are characterized by formation of atubular glomeruli, tubular atrophy and interstitial fibrosis. Thus, the lithium model may be useful in studies of progressive renal diseases, especially tu...

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Development of Hypertension and Life Span in Stroke-Prone Spontaneously Hypertensive Rats During Oral Long-Term Treatment with Various Antihypertensive Drugs

Cited by 19 publications

References 0 publications

Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis

Selective chloride loading is pressor in the stroke-prone spontaneously hypertensive rat despite hydrochlorothiazide-induced natriuresis

Early-Onset But Not Late-Onset Endothelin-A–Receptor Blockade Can Modulate Hypertension, Cerebral Edema, and Proteinuria in Stroke-Prone Hypertensive Rats

Effects of Perindopril and Hydrochlorothiazide on the Long‐Term Progression of Lithium‐Induced Chronic Renal Failure in Rats

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