Cardiac mass and peripheral vascular structure in hydralazine-treated spontaneously hypertensive rats.

Jespersen, Lennard Tang; Nyborg, Niels C. Berg; Pedersen, Ole Lederballe; Mikkelsen, E.; Mulvany, Michael J.

doi:10.1161/01.hyp.7.5.734

Cited by 44 publications

(16 citation statements)

References 39 publications

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“…These doses have been shown to lower arterial pressure significantly when given chronically to SHR. 9 ' 10 On days when tail-cuff pressure was measured, the drugs were given after the measurement was made.…”

Section: Methodsmentioning

confidence: 99%

Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.

Kline

Mercer

1987

Hypertension

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SUMMARY Angiotensin I converting enzyme inhibitors are typically classified as peripheral vasodilators. We studied the effect of captopril and a known vasodilator, hydralazine, on arterial pressure-urinary output relationships in adult spontaneously hypertensive rats to determine whether these drugs produced similar changes in this relationship. Tail-cuff pressure and 24-hour urine output and sodium excretion were measured under steady state conditions during ingestion of tap water or saline (1% NaCI) ad libitum. Sodium intake increased seven to nine times when rats drank saline, but in the absence of drug treatment, tail-cuff pressure was not altered significantly (water, 213 ± 3 vs saline, 220 ± 5 mm Hg). Daily administration of captopril (100 mg/kg p.o.) or hydralazine (15 mg/kg p.o.) for 2 weeks lowered tail-cuff pressure significantly (175 ± 3 and 166 ± 3 mm Hg, respectively; p<0.01) while rats drank tap water. Continued administration of hydralazine plus 2 weeks of drinking saline did not alter tail-cuff pressure (162 ± 4 mm Hg), but with the addition of saline during captopril treatment, tail-cuff pressure was elevated significantly (210 ± 5 mm Hg; p<0.01). Thus, hydralazine produced a parallel shift of the arterial pressure-urinary output relationship along the pressure axis. In contrast, captopril produced a marked change in the slope of this relationship, making arterial pressure extremely salt-sensitive. The results suggest that the two drugs have different effects on the mechanisms that contribute to the long-term control of arterial pressure. The changes associated with captopril treatment are consistent with the removal of the normal renal effects of the renin-angiotensin system, rather than with a nonspecific peripheral vasodilation. (Hypertension 10: 590-594, 1987) KEY WORDS • renal function curve • sodium excretion • sodium sensitivity antihypertensive drugs • captopril • spontaneously hypertensive rats A LTHOUGH numerous types of drugs are effec-/ \ tive in treating primary hypertension, the A. \ -physiological changes leading to the decrease in arterial pressure during administration of these drugs are not well documented. One of the major obstacles to understanding the mechanism of action of antihypertensive agents is the failure to adequately describe the pathophysiology of hypertension. Using a systems analysis approach, Guyton et al.1 have provided a useful conceptual framework for understanding the long-term control of the circulation in normal and abnormal conditions, including hypertension. According to the predictions of their model, the ability of Received March 27, 1987; accepted July 15, 1987. the kidneys to excrete sodium and water is a primary determinant of the long-term steady state level of arterial pressure. 2 -3 The importance of pressure-diuresis and pressure-natriuresis to the long-term control of arterial pressure has recently been reviewed. 4 This relationship between arterial pressure and excretion of sodium and water by the kidneys, called the renal function curve...

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Section: Methodsmentioning

confidence: 99%

Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.

Kline

Mercer

1987

Hypertension

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“…20 -34 Hydralazine has been reported to be less effective than ACE inhibitors in preventing arterial hypertophy. 36 - 37 In SHR, hydralazine was not able to prevent the development of mesenteric or renal artery hypertrophy despite a significant decrease in blood pressure. 37 - 38 However, Owens 34 showed that in the aorta the efficacy of hydralazine and captopril in preventing the development of medial hypertrophy was the same as their efficacy in lowering blood pressure.…”

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“…36 - 37 In SHR, hydralazine was not able to prevent the development of mesenteric or renal artery hypertrophy despite a significant decrease in blood pressure. 37 - 38 However, Owens 34 showed that in the aorta the efficacy of hydralazine and captopril in preventing the development of medial hypertrophy was the same as their efficacy in lowering blood pressure. These discrepancies are consistent with the observation that the aorta, a rather elastic artery, is mainly sensitive to blood pressure changes, 2 whereas in peripheral arteries, which are rather muscular, hypertrophy may be modulated mainly by nonhemodynamic factors 37 -38 such as autonomic nervous system activity.…”

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“…37 - 38 However, Owens 34 showed that in the aorta the efficacy of hydralazine and captopril in preventing the development of medial hypertrophy was the same as their efficacy in lowering blood pressure. These discrepancies are consistent with the observation that the aorta, a rather elastic artery, is mainly sensitive to blood pressure changes, 2 whereas in peripheral arteries, which are rather muscular, hypertrophy may be modulated mainly by nonhemodynamic factors 37 -38 such as autonomic nervous system activity. Therefore, stimulation of this system after hydralazine administration could be responsible for the lack of an antihypertrophic effect at the side of the peripheral arteries.…”

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Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats.

et al. 1994

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Four groups of 4-week-old spontaneously hypertensive rats were treated during 4 months with the angiotensin converting enzyme inhibitor quinapril at 1 mg/kg per day (Ql) or 10 mg/kg per day (Q10), hydralazine at 15 mg/kg per day (H), or placebo (P). In the first set of experiments, blood pressure was measured in conscious rats, and plasma and aortic angiotensin converting enzyme activities were evaluated. In the second set of experiments, histomorphometric parameters of the thoracic aorta were evaluated. Mean blood pressure was lower in the Q10 and H groups (136±16 and 149±11 mm Hg) compared with the P group (190±23 mm Hg) (P<.01). The Ql group showed mean blood pressure values (171 ±15 mm Hg) lower than the P group (P<.05) but significantly higher than the Q10 and H groups (P<.01 and P<.05, respectively). Aortic medial cross-sectional area was significantly lower in the H and Q10 groups (455 ±61 and 487±57 x 10 3 jun 2 ) than in the P group (636±72 /mm of aorta). Aortic angiotensin converting enzyme activity was inhibited by approximately 60% in both groups treated with quinapril, whereas plasma angkrtension converting enzyme activity was reduced only in the Q10 rats. These results show that, whereas both hydralazine and quinapril prevented the development of aortic hypertrophy in a pressure-dependent manner, the prevention of the increase in aortic collagen was observed only after quinapril treatment. This latter effect of angiotensin converting enzyme inhibition was not related to the blood pressure reduction but was associated with the reduction of aortic and not plasma converting enzyme.

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“…14 In contrast, hydralazine does not prevent hypertrophy in other vascular beds. 15 - 17 The second goal was to determine whether antihypertensive treatment attenuates reductions in external, as well as internal, diameter of cerebral arterioles. Because reductions in external diameter can be accompanied by hypertrophy of the vessel wall, 7 we predicted that if antihypertensive treatment prevented hypertrophy, it would also prevent remodeling.…”

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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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Cardiac mass and peripheral vascular structure in hydralazine-treated spontaneously hypertensive rats.

Cited by 44 publications

References 39 publications

Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.

Effect of captopril and hydralazine on arterial pressure-urinary output relationships in spontaneously hypertensive rats.

Angiotensin converting enzyme inhibition prevents the increase in aortic collagen in rats.

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

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