Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats

Rubin, Bernard; Antonaccio, Michael J.; Goldberg, M. E.; Harris, Don N.; Itkin, Arthur G.; Horovitz, Zola P.; Panasevich, Robert; Laffan, Robert J.

doi:10.1016/0014-2999(78)90429-6

Cited by 59 publications

(15 citation statements)

References 21 publications

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“…improves aortic distensibility as shown captopril and hydrochlorothiazide may have a specific effect ise wave amplification in anaesthetized on aortic rigidity. in pulse wave velocity, in the absence of Our observation that in the group treated with captopril on arterial blood pressure, in pithed plus hydrochlorothiazide, the antihypertensive effects of the ;ult suggests that the combination of representatives of two separate classes of drugs are additive is interesting but not original (Rubin et al, 1978;Oster & Epstein, 1987). The explanation generally given for this synergistic effect is stimulation by the diuretic of the reninangiotensin-aldosterone axis, possibly following diureticinduced salt and water loss (Miyamoto et al, 1983).…”

Section: Resultsmentioning

confidence: 98%

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat

Chillon¹,

Capdeville-Atkinson²,

Lartaud³

et al. 1992

British J Pharmacology

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Adult male spontaneously hypertensive rats (SHR) were given captopril plus hydrochlorothiazide mixed in the diet for 10 weeks. Calculated daily doses were 44 mg kg−1 per day for captopril, and 22 mg kg−1 per day for hydrochlorothiazide. Separate groups received captopril or hydrochlorothiazide alone, at similar doses, or no treatment. A final group of WKY normotensive rats received no drug. Systolic arterial blood pressure, measured at regular intervals throughout the 10 weeks' period was lowered but not normalized, in groups receiving either captopril plus hydrochlorothiazide, or captopril alone, but not in the group receiving hydrochlorothiazide alone. Following pentobarbitone anaesthesia, systolic arterial blood pressure, measured in the femoral artery, was found to be lower in all treated groups, but the greatest effect was observed in SHR previously treated with captopril plus hydrochlorothiazide. Aortic pulse wave velocity was also lower in treated SHR, and once again the greatest decrease was observed in the group previously treated with captopril plus hydrochlorothiazide. Following pithing, systolic arterial blood pressures were similar in all SHR groups. Aortic pulse wave velocity was lower in pithed rats previously treated with captopril and hydrochlorothiazide. In conclusion, antihypertensive treatment of SHR produces falls in blood pressure and pulse wave velocity, an indicator of aortic distensibility. Results in pithed rats suggest that treatment with the combination of captopril plus hydrochlorothiazide may increase aortic distensibility independently of blood pressure.

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Section: Resultsmentioning

confidence: 98%

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat

Chillon¹,

Capdeville-Atkinson²,

Lartaud³

et al. 1992

British J Pharmacology

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“…Since their advent, captopril and losartan have been used extensively as antihypertensive agents because of their ability to inhibit Ang II generation and interaction with the AT 1 -R, respectively (Rubin et al, 1978;Celik et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Captopril was first described in 1978 as a chronic antihypertensive agent in hypertensive rats by inhibiting the conversion of Ang I into Ang II by ACE (Rubin et al, 1978). Losartan was introduced later as an alternative to captopril for the treatment of hypertension (Celik et al, 1995).…”

mentioning

confidence: 99%

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Godoy

Rattan

2006

J Pharmacol Exp Ther

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The present study determined the effects of the angiotensinconverting enzyme (ACE) inhibitor captopril and angiotensin II receptor subtype 1 (AT 1 -R) antagonist losartan on the internal anal sphincter pressures (IASP) in spontaneously hypertensive rats (SHR) versus normotensive Wistar-Kyoto rats (WKY). The SHR had significantly higher IASP (21.7 Ϯ 0.8 mm Hg) than the WKY (14.7 Ϯ 0.9 mm Hg), which was associated with the higher levels of angiotensin II (Ang II) in plasma (50.3 Ϯ 0.9 pg/ml) and in muscle bath perfusates (72.7 Ϯ 11.8 pg/ml) compared with the WKY (p Ͻ 0.05). Captopril and losartan decreased the IASP in SHR and WKY, but they were more potent in SHR. Captopril and losartan normalized the IASP in the SHR, whereas these agents may compromise rectoanal continence in the WKY. Reverse transcriptase-polymerase chain reaction and Western blots showed higher levels of angiotensinogen, renin, ACE, and AT 1 -R in the internal anal sphincter (IAS) of SHR. Ang II caused concentration-dependent contraction of IAS smooth muscle strips from WKY (pEC 50 ϭ 8.5 Ϯ 0.1) and SHR (pEC 50 ϭ 8.6 Ϯ 0.2). Losartan (100 nM) significantly (p Ͻ 0.05) inhibited this effect. From these data, we conclude that 1) hypertensive IAS in SHR is primarily the result of renin-angiotensin system upregulation, 2) ACE inhibitors and AT 1 -R antagonists simply relieve the hypertensive IAS, and 3) the differential effect of these inhibitors in the hypertensive versus the normotensive IAS may explain the lack of incontinence as a side effect in hypertensive patients receiving ACE inhibitors and AT 1 -R antagonists.Earlier studies from our laboratory have put forward evidence for the role of angiotensin II (Ang II) biosynthesis in the spontaneous myogenic tone of the internal anal sphincter (IAS) of rats (De Godoy et al., 2004). The studies show the expression of key components of the renin-angiotensin system (RAS

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“…After the development of ACE inhibitors in the 1970s, it became possible to test whether selective interruption of the RAS favorably affects ARAS in animals. Studies by Rubin and colleagues 18,19 showed that captopril (but not hydralazine or hydrochlorothiazide) reduced long-term mortality in ARAS by nearly two thirds. Later work observed improved survival for a range of ACE inhibitors, as well as ARBs, despite some evidence of fibrosis in the clipped kidney ( Figure 1).…”

Section: Angiotensin Inhibitors In Animal Studies Of Arasmentioning

confidence: 99%

Role of Renin-Angiotensin System Blockade in Atherosclerotic Renal Artery Stenosis and Renovascular Hypertension

et al. 2007

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Chronic antihypertensive effects of captopril (SQ 14,225), an orally active angiotensin I-converting enzyme inhibitor, in conscious 2-kidney renal hypertensive rats

Cited by 59 publications

References 21 publications

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat

Chronic antihypertensive treatment with captopril plus hydrochlorothiazide improves aortic distensibility in the spontaneously hypertensive rat

Angiotensin-Converting Enzyme and Angiotensin II Receptor Subtype 1 Inhibitors Restitute Hypertensive Internal Anal Sphincter in the Spontaneously Hypertensive Rats

Role of Renin-Angiotensin System Blockade in Atherosclerotic Renal Artery Stenosis and Renovascular Hypertension

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