Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats.

Stier, Charles T.; Benter, İbrahim F.; Ahmad, Saleem; Zuo, Haillu; Selig, Nicola; Roethel, S.; Levine, Seymour; Itskovitz, Harold D.

doi:10.1161/01.hyp.13.2.115

Cited by 136 publications

(74 citation statements)

References 40 publications

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“…However, in spite of the lack of effect on these cardiovascular variables, ramipril protected against stroke and mortality. In agreement with our observation, Stier et al (1989) also found that, during a high intake of sodium chloride, ACEI treatment decreased SHRSP mortality. The mechanism of this protective effect of ACEI is not clear.…”

Section: Plasma Electrolytes and Renin Activitysupporting

confidence: 93%

Replacement of salt by a novel potassium‐ and magnesium‐enriched salt alternative improves the cardiovascular effects of ramipril

Mervaala

Paakkari

Laakso³

et al. 1994

British J Pharmacology

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1The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2 Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3 Ramipril treatment at a daily dose of 3 mg kg' normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in -the salt group was prevented by ramipril. 4 Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5 Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6 Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria. 7 Our findings suggest that replacement of salt by the potassium-, magnesium-and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.

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Section: Plasma Electrolytes and Renin Activitysupporting

confidence: 93%

Replacement of salt by a novel potassium‐ and magnesium‐enriched salt alternative improves the cardiovascular effects of ramipril

Mervaala

Paakkari

Laakso³

et al. 1994

British J Pharmacology

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“…Enalapril, another ACE inhibitor, reduces stroke in SHRSP that are fed a high salt diet. 45 In this study, stroke was prevented by both cilazapril and hydralazine, even though hydralazine was less effective than cilazapril in reducing mean arterial pressure. Thus, our data suggest that even moderate reductions in mean arterial pressure are effective in preventing stroke in SHRSP.…”

Section: Strokementioning

confidence: 60%

Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats.

1991

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The purpose of this study was to examine effects of antihypertensive treatment on structure and mechanics of cerebral arterioles and the incidence of stroke in stroke-prone spontaneously hypertensive rats (SHRSP). Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day). Cilazapril and hydralazine reduced systolic arterial pressure (from 195±8 to 125±5 and 148±3 mm Hg, respectively [mean±SEM]; p<0.05). To examine structure and mechanics of cerebral arterioles, we measured pressure (servonull), external diameter, and cross-sectional area of the vessel wall (histologically) in pial arterioles of normotensive Wistar-Kyoto (WKY) rats and SHRSP that were untreated or that were treated for 3 months with cilazapril or with hydralazine. Arterioles were maximally dilated with EDTA. In WKY rats, cilazapril and hydralazine did not alter pial arteriolar pressure, external diameter, or cross-sectional area of the vessel wall. In SHRSP, both cilazapril and hydralazine reduced cross-sectional area of the vessel wall to levels not significantly different from WKY rats (from 1,911±155 to l,244±101 and l r 388±59 /im\ respectively, compared with l,405±95 /tm 2 for untreated WKY rats). Cilazapril was more effective than hydralazine in reducing pial arteriolar pressure (from 110 ±6 to 62 ±2 mm Hg with cilazapril versus 79 ±5 mm Hg for hydralazine compared with 60±4 mm Hg for untreated WKY rats). Cilazapril, but not hydralazine, attenuated reductions in external diameter of pial arterioles (from 91 ±4 to 100 ±4 (tm for cilazapril versus 91 ±3 fim for hydralazine compared with 107 ±3 fim for untreated WKY rats). Stress-strain curves indicate that cilazapril was more effective than hydralazine in attenuating increases in distensibility of pial arterioles in SHRSP. Both treatments prevented the occurrence of stroke in SHRSP, whereas eight of 15 untreated SHRSP developed strokes. Thus, both an ACE inhibitor and hydralazine prevented hypertrophy of cerebral arterioles and stroke in SHRSP, even though the ACE inhibitor was more effective than hydralazine in lowering intra-arteriolar pressure. In contrast, only the ACE inhibitor attenuated increases in distensibility and "remodeling" (reduction in external diameter) of cerebral arterioles, perhaps due to its greater efficacy in reducing pial arteriolar pressure at the doses used in this study. These findings suggest that determinants of distensibility and vascular remodeling may be different from determinants of vascular hypertrophy. (Hypertension 1991;17:308-316) C hronic hypertension alters the composition and mechanics of both large and small cerebral blood vessels. Large cerebral arteries undergo hypertrophy, with an increase in collagen content, and compliance is reduced in spontaneously hypertensive rats (SHR) 12 and stroke-prone SHR (SHRSP). 34 In contrast, compliance of cerebral arterioles is paradoxically increased in SHRSP, despite

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“…Similar improvement in animal survival independent of blood pressure effects has been demonstrated in a group of nondiabetic, salt-loaded, stroke-prone SHR treated with enalapril. 17 Other studies have shown that treatment with ACE inhibitors reduces blood pressure and prolongs life in experimental models of renal failure. 1315 Long-term intracerebral treatment with captopril can reduce the salt appetite in SHR.…”

Section: Discussionmentioning

confidence: 99%

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

1991

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To establish if the benefit of angiotensin converting enzyme inhibitor therapy in retarding progressive diabetic renal injury is due to a specific intrarenal effect or the systemic hypotensive effect, we studied the effect of long-term ramipril treatment on blood pressure, glomerular filtration rate, and urinary protein excretion in streptozotocin-diabetic spontaneously hypertensive rats. The hypotensive effect of ramipril was prevented by a high salt diet, which did not alter the degree of renal angiotensin converting enzyme inhibition. Three weeks after uninephrectomy and induction of diabetes, rats were allocated to three groups. Groups 1 and 2 were given 1% NaCl, whereas group 3 was given water as drinking solution. One week later, groups 2 and 3 received 0.4 mg/kg/day ramipril in their drinking solution, which was continued over a 2-month period. Ramipril produced a blood pressure fall only in water-drinking rats (group 3) despite a similar reduction in plasma and renal angiotensin converting enzyme activity in groups 2 and 3. Salt-loaded rats had a progressive increase in urinary protein excretion over the duration of study. Ramipril treatment prevented an increase in protein excretion only in animals given water and with a reduced systolic blood pressure. Glomerular nitration rate was similar in all three groups. Ramipril treatment improved animal survival independently of a reduction in blood pressure or an effect on proteinuria. Although it is possible that angiotensin converting enzyme inhibitors have specific intrarenal effects reducing progression of diabetic proteinuria, concomitant control of systemic blood pressure appears to be necessary to demonstrate a benefit. (Hypertension 1991;17:497-503) U ncontrolled systemic hypertension is a wellknown cause of progressive renal injury in both humans and experimental animals. 1Hypertension is commonly associated with diabetic renal disease,'-3 and it has been shown to accelerate the rate of development of diabetic nephropathy both in humans 4 and in streptozotocin-diabetic rats. 13 or in other renal disorders. 1415 However, it is difficult to determine from these studies if the beneficial effect of ACE Received February 9, 1990; accepted in revised form November 29, 1990. inhibitors was due to a specific intrarenal effect of ACE inhibition or due to their systemic hypotensive effect.To evaluate this question further, we examined the effect of long-term administration of the ACE inhibitor ramipril on blood pressure, glomerular filtration rate, and proteinuria in streptozotocin diabetic uninephrectomized spontaneously hypertensive rats (SHR). To prevent the hypotensive effect of ACE inhibition, the rats were maintained on a high salt diet, which is known to oppose the blood pressurelowering action of ACE inhibitors. -17 Methods Study Protocol

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Enalapril prevents stroke and kidney dysfunction in salt-loaded stroke-prone spontaneously hypertensive rats.

Cited by 136 publications

References 40 publications

Replacement of salt by a novel potassium‐ and magnesium‐enriched salt alternative improves the cardiovascular effects of ramipril

Replacement of salt by a novel potassium‐ and magnesium‐enriched salt alternative improves the cardiovascular effects of ramipril

Effects of antihypertensive therapy on mechanics of cerebral arterioles in rats.

Salt blocks the renal benefits of ramipril in diabetic hypertensive rats.

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