Effects of Lisinopril on the Structure of Renal Arterioles

Notoya, Mitsuru; Nakamura, Masuhisa; Mizojiri, Kenji

doi:10.1161/01.hyp.27.3.364

Cited by 33 publications

(30 citation statements)

References 41 publications

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“…This is compatible with another recent study showing that the afferent arteriolar diameter is greater in ACEI-treated SHR compared with nontreated controls. 25 Analyzed together with our previous findings, these results suggest that ACEI remodels the same amount of vascular wall around a greater lumen. Expressed in terms of remodeling, the observed vascular changes can be described as outward, eutrophic remodeling.…”

Section: Discussionsupporting

confidence: 78%

Perindopril Treatment Affects Both Preglomerular Renal Vascular Lumen Dimensions and In Vivo Responsiveness to Vasoconstrictors in Spontaneously Hypertensive Rats

et al. 1998

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Abstract-We have previously shown that chronic treatment with angiotensin-converting enzyme inhibition (ACEI) did not reverse hypertrophy of the renal arterial wall in spontaneously hypertensive rats (SHR). In this study we determined the effects of perindopril on the functional properties of the renal vasculature in vivo and on its resistance to flow at maximal dilatation in vitro, a measure of vessel lumen diameter. Two groups of SHR were studied: untreated or treated with perindopril (3 mg/kg per day) in their drinking water from 4 weeks of age. At 10 weeks, (1) vessel lumen characteristics were assessed using a maximally dilated in vitro isolated kidney perfusion and (2) the renal vasoconstrictor responses to bolus doses of vasoactive agents (angiotensin II and phenylephrine) administered into the renal artery were measured in vivo (anesthetized rats). Mean arterial pressure was significantly lower in conscious SHR treated with perindopril (132Ϯ2 versus 97Ϯ2 mm Hg, PϽ.001). In vitro, the pressure-flow relationship and the pressure-glomerular filtration rate relationship were both shifted significantly to the left (PϽ.001). The perindopriltreated kidneys began filtering at a significantly lower threshold perfusion pressure than nontreated controls (PϽ.001).In vivo, renal vasoconstrictor responses to increasing doses of both vasoconstrictor agents were significantly less marked in the perindopril-treated SHR than in untreated SHR (PϽ.05). Thus, chronic ACEI increased average renal vessel lumen diameter in SHR, predominantly in preglomerular vessels, and reduced renal vasoconstrictor responsiveness in vivo, findings compatible with remodeling of the preglomerular vasculature around a greater lumen. (Hypertension. 1998;31:1007-1013.)Key Words: angiotensin-converting enzyme inhibitors Ⅲ kidney Ⅲ perfusion Ⅲ rats, inbred SHR Ⅲ vascular resistance T he walls of the preglomerular vessels of the SHR are thicker than those of the normotensive Wistar-Kyoto rat 1-3 and their vascular lumen is narrower. [3][4][5][6][7][8] We have shown that treatment with an ACEI from weaning did not appear to reduce wall thickening of the interlobular and arcuate arteries in SHR vessels despite normalization of blood pressure.2 This is in contrast to the known effects of chronic ACEI treatment in other vascular beds. 9 -11 Our previous study of the renal vessel response to ACEI was stereological, with kidneys fixed at physiological pressure.2 While this study provided accurate estimates of wall dimensions, it did not provide reliable lumen dimensions. This was due to the fact that the prevailing physiological conditions will have determined smooth muscle tone, and therefore vessel radius, and because of possible fixation artifacts. Thus, it was not possible in this morphometric study to document whether the wall hypertrophy had resulted in lumen encroachment or to determine how the wall dimensions affected renal vascular properties in vivo.The aim of the present study was to determine the effects of chronic ACEI treatment on the rena...

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Section: Discussionsupporting

confidence: 78%

Perindopril Treatment Affects Both Preglomerular Renal Vascular Lumen Dimensions and In Vivo Responsiveness to Vasoconstrictors in Spontaneously Hypertensive Rats

et al. 1998

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“…32 In our study, losartan did not reduce media hypertrophy as much as enalapril did. Previous treatment with ACE inhibitors showed an increase in the diameter of renal afferent arteriole 33 or a large mesenteric artery. 34 An increase in the lumen is known to increase the average circumferential wall stress, which may also provide nonspecific stimulus hypertrophy in SHR treated with losartan.…”

Section: Discussionmentioning

confidence: 93%

Interaction of mRNAs for Angiotensin II Type 1 and Type 2 Receptors to Vascular Remodeling in Spontaneously Hypertensive Rats

et al. 1998

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Abstract-We administered angiotensin II (Ang II) receptor type 1 (AT 1 ) blockade (losartan, 40 mg ⅐ kg Ϫ1 ⅐ d Ϫ1), type II receptor (AT 2 ) blockade (PD123319, 100 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ), or angiotensin-converting enzyme (ACE) inhibitor (enalapril, 30 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 ) to spontaneously hypertensive rats (SHR) from 10 to 20 weeks of age. Control SHR and Wister-Kyoto rats (WKY) received a placebo for the same period. At the end of treatment, losartan and enalapril were both found to have significantly reduced the arterial systolic blood pressure and the collagen concentration to the level of WKY, whereas PD123319 had no effect. Enalapril and PD123319 significantly reduced the media cross-sectional area of the aorta in comparison to that of untreated SHR, which was still larger than that of the WKY; however, losartan did not change it. Using reverse transcription-polymerase chain reaction, we next examined the mRNA expressions for ACE, AT 1 receptor, and AT 2 receptor in experimental animals. We observed significantly enhanced mRNA expression for AT 1 and AT 2 receptors and ACE in untreated SHR compared with WKY. The AT 1 mRNA level was also significantly decreased in the SHR treated with either losartan or enalapril, whereas the AT 2 mRNA level was significantly decreased in the SHR treated with either PD123319 or enalapril in comparison to untreated SHR. The level of ACE mRNA was significantly decreased only in the SHR treated with enalapril. These results indicate that AT 1 receptor, but not AT 2 receptor, plays a crucial role in the remodeling of matrix tissue, while AT 2 receptor may play a role in the development of hypertrophy of smooth muscle in aorta in SHR, and that the reduction of hypertrophy of smooth muscle does not fully account for the suppression of hypertension. (Hypertension. 1998;32:467-472.) Key Words: angiotensin II Ⅲ receptors, angiotensin Ⅲ hypertrophy, vascular Ⅲ collagen Ⅲ rats, inbred SHR L ong-term hypertension is reported to be associated with cardiovascular remodeling, which consists of cardiovascular hypertrophy and an increase in the extracellular matrix (especially collagen).1,2 In spontaneously hypertensive rats (SHR), both left ventricular hypertrophy and the properties of characteristic vascular resistance are already present early in life, based on the results of a comparison with normotensive Wister-Kyoto rats (WKY).3,4 Angiotensin-converting enzyme (ACE) inhibitors can lower the blood pressure in SHR mainly by reducing the production of angiotensin II (Ang II).5 Ang II is considered to act as a growth-promoting factor in aortic smooth muscle cells, 6,7 while it also increases collagen synthesis in smooth muscle cells.8 ACE inhibitors suppress such vascular remodeling in experimental models, possibly through blood pressure-independent mechanisms. 9,10 Recently, a selective Ang II receptor antagonist has been developed that inhibits the renin-angiotensin system (RAS) more specifically than ACE inhibitors. Two main Ang II receptor subtypes, AT 1 and AT 2 , have been identified, a...

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“…In the SHR, and presumably also in the SHRSP, hypertension is likely caused by a genetically determined narrowing of the renal afferent arteriole 29 -31 that is susceptible to physiological 32 and pharmacological modulation. 33,34 In the SHR, pharmacological inhibition of the angiotensin converting enzyme dose-dependently attenuates hypertension and the narrowing of the renal afferent arteriole, 33,34 the extent of narrowing varying directly with the severity of pharmacologically attenuated hypertension. 33 Even in the normal rat, Cl Ϫ selectively loaded either in the diet 13,14 or in the isolated perfused kidney 35 induces renal vasoconstriction and amplifies that induced by angiotensin II, 14,36 likely by constricting the renal afferent arteriole 37 such that glomerular filtration rate is reduced.…”

Section: Discussionmentioning

confidence: 99%

Chloride-Dominant Salt Sensitivity in the Stroke-Prone Spontaneously Hypertensive Rat

et al. 2005

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Abstract-We tested the hypothesis that in the stroke-prone spontaneously hypertensive rat (SHRSP), the Cl Ϫ component of dietary NaCl dominantly determines its pressor effect (salt-sensitivity). We telemetrically measured systolic aortic blood pressure (SBP) in SHRSP loaded with: nothing (CTL); NaCl alone (NaCl) (44 mmol/100 grams chow); KCl (KCl) alone (44 mmol); NaCl (44 mmol) combined with KHCO 3 (77 mmol) (NaCl/KBC) or with KCl (77 mmol) (NaCl/KCl). Across all groups, from age 10 to 15 or 16 weeks, SBP increased linearly (mm Hg/week) (dp/dt, change in SBP as a function of time): CTL, 5.6; NaCl, 9.5; KCl, 8.8; NaCl/KBC, 9.1; and NaCl/KCl, 14.6. Thus, the value of dp/dt in KCl matched that in NaCl. The value of dp/dt in NaCl/KCl exceeded that in NaCl in direct proportion to the greater Cl Ϫ load. Across all groups, only Cl Ϫ load bore a direct, highly linear relationship with dp/dt. Strokes occurred only, but always with SBP Ͼ250 mm Hg, a value observed almost exclusively in NaCl/KCl. Thus, Cl Ϫ dominantly determined the pressor effect induced with dietary NaCl, both with NaCl loaded alone and combined with either KCl or KHCO 3 , and thereby likely determined the occurrence of stroke with NaCl loading. Over the initial 3-day period of NaCl loading and exacerbating hypertension, external balance of Na ϩ increased similarly among all groups. However, within 24 hours of initiating NaCl loading, urinary creatinine excretion decreased in direct proportion to dp/dt and urinary Cl Ϫ excretion. We conclude that in the SHRSP, the Cl Ϫ component of a dietary NaCl dominantly determines salt sensitivity and thereby phenotypic expression. We suggest that Cl

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Effects of Lisinopril on the Structure of Renal Arterioles

Cited by 33 publications

References 41 publications

Perindopril Treatment Affects Both Preglomerular Renal Vascular Lumen Dimensions and In Vivo Responsiveness to Vasoconstrictors in Spontaneously Hypertensive Rats

Perindopril Treatment Affects Both Preglomerular Renal Vascular Lumen Dimensions and In Vivo Responsiveness to Vasoconstrictors in Spontaneously Hypertensive Rats

Interaction of mRNAs for Angiotensin II Type 1 and Type 2 Receptors to Vascular Remodeling in Spontaneously Hypertensive Rats

Chloride-Dominant Salt Sensitivity in the Stroke-Prone Spontaneously Hypertensive Rat

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