ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The precise contribution of the renin-angiotensin system to the genesis of essential hypertension is difficult to discern from clinical studies with converting enzyme inhibitors because of their multiple pharmacological effects. Specific inhibitors of renin, appropriate for clinical investigation, would help to resolve this question. Four classes of compounds have been demonstrated to be renin inhibitors of high potency: specific antibodies, general peptide inhibitors of acid proteases, analogues of angiotensinogens, and peptides related to the amino-terminal sequence of prorenin. Of these, it is likely that angiotensinogen analogues will be the first to be applied in human studies. The minimal substrate for renin has the sequence: His-Pro-Phe-His-Leu-Leu-Val-Tyr. Variants of this sequence have yielded competitive inhibitors. Recently, remarkably active compounds have been synthesized by reducing the peptide bond cleaved by renin or by incorporating the amino acid statine, found in pepstatin. These compounds have now been shown to be effective in dogs, rats and monkeys, and, according to recent preliminary studies, in man.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

125I labelled mouse submaxillary renin was administered intravenously to anaesthetized male Institute of Cancer Research, USA (ICR) mice in an attempt to determine the organ-related degradation of circulating renin. A specific antirenin antiserum was used for identification. The disappearance rate of labelled renin from plasma was estimated on the basis of a two-compartmental model. The mean half-time of clearance of labelled renin from plasma in intact control and 70% hepatectomized mice was 13.3 ± 0.8 and 12.0 ± 0.9 min respectively; these values were not significantly different. The mean half-time of clearance of labelled renin from plasma in nephrectomized mice was 40.0 ± 2.4 min; this was significantly longer than intact controls and 70% hepatectomized mice. Fifty per cent of the administered renin accumulated in the kidney and 9% in the liver. A small amount of125I labelled renin was identified in urine, and a large amount of125I liberated from labelled renin was detected. Since the high performance liquid chromatography profiles showed that plasma renin rapidly moves into the kidney, clearance of circulating renin may take place mainly in this organ.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Alpha2adrenoreceptors are located on vascular smooth muscle of the rat tail artery. In the present study this receptor was studied in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Adrenergic agonists were used to produce isometric contractions of helically-cut tail artery strips from SHR and WKY. Clonidine and guanabenz, alpha2agonists, were more potent in the SHR than in the WKY (e.g. clonidine: EC50SHR = 3.5 ± 0.6 × 10-8M; EC50WKY = 17.0 ± 0.2 × 10-8M;P< 0.0005). There was no difference in potency between the alpha1agonists, phenylephrine and methoxamine. Yohimbine, an alpha2antagonist, was more potent in inhibiting the clonidine-induced contraction in the SHR (pA2= 7.66 versus 7.14). To determine the number of alpha2adrenoreceptors, the specific binding of3H-clonidine to homogenates of tail artery and of five brain areas was also measured. The maximum number of high-affinity sites on the tail artery was threefold greater in SHR than in WKY (31 ± 5 versus 11 ± 3 fmol/mg protein,P< 0.0005). No differences in the number or affinity of alpha2receptor sites was found in the hypothalamus, hippocampus, locus coeruleus or parietal cortex of the two strains of rat. There was a difference in the amygdala (SHR: 163 ± 16 versus WKY: 108 ± 14,P< 0.05). The larger number of alpha2adrenoreceptors on the vascular smooth muscle in SHR may provide an explanation for the supersensitivity of SHR to adrenergic agonists.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Baroreflex control of heart rate in response to phenylephrine was studied in conscious Sabra hypertension-prone (SBH) rats, at a prehypertensive stage, and hypertension-resistant (SBN) rats. Baroreflex sensitivity as determined From the slope of the relationship of mean arterial blood pressure and heart period was significantly lower in SBH rats (0.58 ± 0.06 versus 1.71 ± 0.11 ms/mmHg in SBN rats,P< 0.01) before the development of hypertension. Sympathetic nerve blockade with guanethidine (15 mg/kg) significantly reduced the slope of the mean arterial blood pressure-heart period relationship in SBN rats to 0.45 ± 0.05 ms/mmHg (P< 0.01) and increased the pressor response to phenylephrine, without having any effect on these parameters in SBH rats. Atropine methyl nitrate (1 mg/kg) abolished reflex vagal bradycardia in response to phenylephrine in both groups of rats. This suggests that SBH rats are unable to withdraw the sympathetic cardiac component of the baroreflex in response to a pressor stimulus and appear to rely only on increased vagal activity to effect bradycardia.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The influence of sex, age, blood pressure and physical stress on β2-adrenoceptor density on intact mononuclear cells was investigated in normotensives and in patients with essential hypertension using (±) 125-iodocyanopindolol as radio-ligand.The intra-individual receptor status under basal conditions at rest was fairly constant. The mean individual deviation of β2-adrenoceptor density was 11% after a time period of 3 ± 1.9 months.The receptor number increased with age: there was a positive correlation (r = 0.59) between age and β2-adrenoceptor density. No significant difference existed between men and women matched for age and mean arterial blood pressure (548 ± 179 versus 481 ± 246 maximal binding sites per cell).A highly significant positive correlation (r = 0.73) existed between the mean arterial blood pressure and the β2-adrenoceptor density over a wide range of normal and increased blood pressure.A factorial analysis revealed a significant correlation between mean arterial pressure and β2-adrenoceptor density, but not between age or sex and β2-adrenoceptor density.Physical stress led within 15 min to a significant increase in β2-adrenoceptors followed by a fall to or even below the starting values after 15 to 30 min rest.It is concluded that β2-adrenoceptor density on intact mononuclear cells correlates significantly with mean arterial blood pressure and with age. However, factorial analysis revealed a significant positive correlation only between mean arterial blood pressure and the receptor number but not between age and the receptor number. Sex has no significant influence on the receptor density.The observed rapid increase of β2-adrenoceptors under physical stress is possibly due to an acute activation of preformed inactive β2-binding sites.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

The influence of dietary modification of polyunsaturated fatty acids (PUFA) on renin secretion, renal vascular tone and prostanoid excretion was studied in isolated perfused rat kidneys under basal conditions and in response to angiotensin II. After a four-week regimen of diets enriched with safflower oil, linseed oil or saturated fat, providing 20% of total energy intake (20 energy %), the animals which were fed linseed oil showed a significant fall in the proportion of arachidonic acid in renal phospholipids and a reduction in urinary prostaglandin excretion. In comparison with the other dietary groups, linseed oil feeding also resulted in a consistently lower renal vascular tone with increasing doses of angiotensin II. Under basal conditions both the PUFA-fed groups had significantly lower renal venous renin secretion rates relative to the saturated fat-fed control group. Infusion of angiotensin II (10 ng/min) suppressed renin secretion and abolished significant differences between the groups. As both the control group and the safflower oil group excreted similar levels of urinary prostaglandins, these results suggest that dietary enrichment with 20 energy % PUFA alters renin secretion by a prostaglandin-independent mechanism and that this may contribute to the lower blood pressures observed in these animals compared with the saturated fat-fed control group.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

Active and inactive renin have been studied in peritoneal fluid and plasma of six patients with ascites and four patients on peritoneal dialysis (using concentrated dialysate). Acid-pepsin and trypsin activation gave similar results. In ascitic patients mean (± s.e.) plasma active renin was very high (0.31 ± 0.99 pmol angiotensin l/l/s) compared with normal subjects (0.31 ± 0.08 pmol ANG l/l/s). Plasma inactive renin (1.27 ± 0.30 pmol ANG l/l/s) was similar to normal subjects (1.31 ± 0.31 pmol ANG l/l/s) while the mean percentage of total renin which was inactive was 29.7 and 76.5. In ascitic fluid, active renin was very low (0.36 ± 0.09 pmol ANG l/l/s) but inactive renin (2.15 ± 0.28 pmol ANG l/l/s) was higher than plasma. Percentage of total renin inactive was 85.8. Peritoneal dialysate showed even smaller amounts of active renin but similar inactive renin with 95.4 per cent inactive (versus 73.8 in their plasma). Peritoneal fluid inactive renin was similar to that in plasma by affigel chromatography and gel filtration and showed, after activation, similar pH optima and Michaelis constants to plasma and peritoneal active renin.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID

摘要:

An inhibitor of angiotensin I (ANG I) converting enzyme, SA446, reduced the response to ANG I of blood vessels isolated from dogs and monkeys, but did not abolish the response even at high concentrations. The residual action of ANG I in the presence of high concentrations of SA446 could be abolished by (Sar1, Ala8)-ANG II. Vascular strips and crude extracts of vessels and lungs possessed the enzymic activity generating ANG II from ANG I, or hippuric acid from hippuryl-histidyl-leucine (HHL). The HHL-hydrolysing activity of the crude extracts was completely inhibited by SA446 (10-7mol/l) and/or Na2-EDTA (10-3mol/l). However, the octapeptide generation was not abolished despite the combined treatment with SA446 (5 × 10-4mol/l) and Na2-EDTA (5 × 10-3mol/l). The residual activity forming ANG II was inhibited by chymostatin and soybean trypsin inhibitor, which however did not affect the HHL-hydrolysis. Combined treatment with SA446 (10-5mol/l) and chymostatin (2.5 × 10-5mol/l) abolished the vascular action of ANG I but did not alter the action of ANG II. These results strongly suggest that besides the ANG I converting enzyme, another enzyme which generates ANG II is present in vascular tissues and lungs, and may play an important role in the local generation of ANG II, which possibly regulates the regional vascular tone.

ISSN:0263-6352    

出版商:OVID    

年代:1984

数据来源: OVID