摘要:

Changes in our concepts of angiotensin I converting enzyme are reviewed briefly. The actions of this enzyme go beyond liberating angiotensin II from angiotensin I or inactivating bradykinin. Its very wide distribution in the body and its activity in vitro indicate involvement in the metabolism of other biologically active peptides. The recent molecular cloning of the human enzyme confirmed the existence of a hydrophobic C-termlnal peptide that forms the short transmembrane domain of this plasma membrane-bound enzyme. The much longer external portion contains two homologous active site domains but probably only one functional active center. Finally, in spite of the great progress made in studying angiotensin converting enzyme, there are many challenging problems waiting to be solved.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

We review below published studies of endothelium-dependent vasodilation in vivo. Endothelium-dependent vasodilation has been demonstrated in conduit arteries in vivo and in the cerebral, coronary, mesenteric, and femoral vascular beds as well as in the microcirculation of the brain and the microcirculation of cremaster muscle. The available evidence, although not complete, strongly suggests that the endothellum-derived relaxing factor generated by acetylcholine in the cerebral microcirculation is a nitrosothiol. The endothelium-derived relaxing factor generated by bradykinin in this vascular bed is an oxygen radical generated in association with enhanced arachidonate metabolism via cyclooxygenase. In the microcirculation of skeletal muscle, on the other hand, the vasodilation from bradykinin is mediated partly by prostacycline and partly by an endothelium-derived relaxing factor similar to that generated by acetylcholine. Basal secretion of endothelium-derived relaxing factor is controversial in vivo but is usually present in vitro. On the other hand, it appears that endothelium-derived relaxing factor mediates flow-dependent vasodilation in both large vessels and in the microcirculation in vivo. The generation and release of endothelium-derived relaxing factor from endothelium may be abnormal in a variety of conditions including acute and chronic hypertension, atherosclerosis, and ischemia followed by reperfusion. Several mechanisms for these abnormalities have been identified. These include inability to generate endothelium-derived relaxing factor or destruction of endothelium-derived relaxing factor by oxidants after its release in the extracellular space. These abnormalities in endothelium-dependent relaxation may contribute to the vascular abnormalities in these conditions.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Thirty-one patients with essential hypertension (81.6±6.9 years old) were studied during two different regimens of sodium intake: 120 meq/day for 8 weeks and 344 meq/day for 2 weeks. Systemic hemodynamic data were measured with Doppler echocardiography from which the mitral flow velocity integral, cardiac index, and total peripheral resistance were calculated. The salt-sensitive patients in whom the increase in total peripheral resistance was greater than the increase in cardiac index with salt loading were termed SSr. In the salt-sensitive patients termed SSC, the increase in cardiac index was greater than the increase in total peripheral resistance with increased sodium intake. All SSr patients on day 7 of the high sodium diet remained in the S&r group on day 14. Nine of 13 patients in the SSC group on day 7 remained in the SSC group on day 14, and the remaining four patients in the SSC group on day 7 fell into the SSr group on day 14. Four of eight non-salt-sensitive (NSS) patients on day 7 of the high salt regimen remained in the NSS group on day 14, whereas the remaining four patients in the NSS group on day 7 fell into the SSC group on day 14. Our data suggest a changing pattern with sodium loading of initially high cardiac index followed by a persistently raised total peripheral resistance. The celiac, superior mesenteric, and renal arteries vasoconstricted with sodium repletion in both SSr and SSC patients. With salt loading, the terminal aortic vascular bed vasodilated in the SSC patients and vasoconstricted in the SSr patients.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The aim of this study was to determine whether moderate restriction of dietary salt intake leads to an additional fall in blood pressure in treated hypertensive men who are asked to simultaneously reduce their usual alcohol intake. Sixty-three subjects entered an initial 2-week familiarization period during which they continued their usual alcohol intake and commenced a “low sodium” diet (less than 60 mmol/day) supplemented with 100 mmol sodium chloride per day as enteric-coated tablets. Subjects were then randomly assigned to either drink a low alcohol beer alone for a 4-week period (reducing their self-reported alcohol consumption from 537 to 57 ml/week) or to continue their usual alcohol intake (543 versus 557 ml/week). Within the low and normal alcohol intake groups, subjects were assigned to either a low or normal sodium intake. The low sodium groups continued the sodium-restricted diet but were switched to placebo sodium chloride tablets for the 4 weeks. This resulted in a fall in the 24-hour urinary sodium excretion from 144 to 69 mmol/day. The normal sodium groups continued the low sodium diet but kept taking 100 mmol/day of the sodium chloride tablets, and their urinary sodium excretion remained unchanged (125 versus 142 mmol/day). Regular antihypertensive therapy was continued throughout Fifty-nine subjects completed the trial. In those who reduced their alcohol intake there was a fall in both systolic blood pressure (‐5.4 mm Hg supine, p<0.01) and diastolic blood pressure (‐3.2 mm Hg supine, p<0.0l). There was no effect of salt restriction on blood pressure and no evidence of an additive effect of alcohol and salt restriction. The results indicate that, in a selected sample of treated hypertensive drinkers, a short-term and moderate reduction in salt intake in addition to a substantial decrease in alcohol intake does not lead to a greater fall in blood pressure than that seen with alcohol restriction alone.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Metabolic addosis has recently been observed in rat models of salt-sensitive genetic hypertension. To test the hypothesis that salt sensitivity in humans may be associated with abnormal acid-base homeostasis, we performed arterial blood gas analyses in young (20–31 years old) normotensive subjects (n=40) who were placed on a low salt diet (20 mmol NaCl/day) for 2 weeks with either 200 mmol sodium chloride or placebo added to the low salt diet for 1 week each in a randomized, single-blind crossover order. Furthermore, a subset of the subjects (seven salt-sensitive and eight salt-resistant) received 200 mmol sodium/day as the citrate salt as a supplement to the low salt diet for a third week. During each regimen, blood pressure as well as arterial pH and bicarbonate levels were measured. Salt sensitivity was defined as a significant drop in mean arterial pressure greater than 3 mm Hg (mean of 30 readings taken during each diet, p< 0.05) while the subject was on the low salt diet According to this definition, 16 subjects were salt-sensitive and 24 salt-resistant During the high sodium chloride regimen, arterial pH and bicarbonate levels were significantly lower in the salt-sensitive than in the salt-resistant group (p<0.0001). The increase in blood pressure caused by sodium chloride correlated inversely to the arterial pH (r= −0.57,p=0.0002) and bicarbonate levels (r= −0.52,p=0.0007) during the high salt diet Sodium chloride increased mean arterial blood pressure in the salt-sensitive subjects; sodium citrate did not Sodium citrate led to an increase in pH and bicarbonate levels in both groups. Our finding that a sodium chloride-induced rise in blood pressure is associated with lower arterial plasma pH and bicarbonate levels points to an abnormality in renal acid-base regulation in salt-sensitive subjects.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Blood pressure and pulse interval are characterized not only by erratic variations but also by rhythmic fluctuations at low-, mid-, and high-frequency (0.025–0.07, 0.07–0.14, and 0.14–0.35 Hz, respectively). However, information on these phenomena has largely been derived from analysis of short-term recordings taken in standardized laboratory conditions. In seven normotensive and 10 untreated mild essential hypertensive subjects, power spectrum analysis was performed on the intra-arterial blood pressure and pulse interval signal collected over a 24-hour period using the fast Fourier transform algorithm and splitting the recording into contiguous segments of 256 beats. About 70% of the segments were suitable for the analysis; the segments excluded for a nonstationary signal amounted to only 30%. All powers were characterized by a high segment-to-segment variability, but in each subject the mid- and high-frequency powers of diastolic blood pressure and the mid-frequency power of systolic blood pressure were markedly reduced during the night as compared with the daytime period, whereas the opposite occurred for the low- and high-frequency powers of the pulse interval. Over the 24-hour period, mid- and high-frequency powers of blood pressure were positively correlated to each other, but both accounted for less than 25% of the 24-hour blood pressure variance. No difference between mean normalized power values of normotensive and hypertensive subjects was observed. Thus, at both normal and mildly elevated blood pressure, rhythmic blood pressure and pulse interval oscillations falling in the low-, mid-, and high-frequency ranges are not masked by the erratic environmental stimuli of daily life but can be identified over most of the 24-hour time period. The magnitude of these phenomena is only a fraction of the overall variability and is subjected to large moment-to-moment modifications. In several circumstances, however, the nighttime period was accompanied by systematic and pronounced changes that may help in determining the mechanisms that underlie these events.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

This study was designed to determine whether diurnal patterns of blood pressure, heart rate, or locomotor activity differed among two substrains of Wistar-Kyoto rats, derived originally from Charles River or Taconic Farms stock, or the spontaneously hypertensive rat Cardiovascular parameters were continuously monitored over 24 hours. Resting systolic and diastolic blood pressure values were statistically different among the three groups both during the lights-on (rest) and lights-off (active) phases of the cycle with blood pressure of spontaneously hypertensive rats greater than that of Wistar-Kyoto rats from Taconic Farms, which was greater than that of Wistar-Kyoto rats from Charles River. The largest difference in arterial pressure between Wistar-Kyoto/Taconic Farms and Wistar-Kyoto/Charles River was during the lights-on period. Heart rates of all rats decreased during the lights-on period; Wistar-Kyoto/ Charles River had the largest decrease (−70±5 beats/min), Wistar-Kyoto/Taconic Farms had the least (‐17±2 beats/min), and in spontaneously hypertensive rats the decrease was intermediate (‐29±3 beats/min). The pronounced diurnal variation in pressure and heart rate exhibited by Wistar-Kyoto/Charles River was not present in either Wistar-Kyoto/Taconic Farms or spontaneously hypertensive rats. Blood pressure magnitude correlated with locomotor activity during both periods, although all groups showed minimal activity during the rest period. Observed differences between Wistar-Kyoto/Charles River and Wistar-Kyoto/Taconic Farms were not due to a lack of or an abnormality in baroreceptor reflex function. Because most investigations that use these rat strains are performed during the lights-on phase of the diurnal cycle, the results demonstrate the need for a careful analysis of individual experimental protocols as well as the determination of the appropriate control for the spontaneously hypertensive rat

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The contribution of endogenous kinins to the acute antihypertensive actions of the converting enzyme inhibitor ramipril was investigated in kinin-deficient Brown Norway rats and in Brown Norway-Hannover rats and Wistar rats as controls. In Brown Norway rats, urinary kinin excretion was measurable but extremely low when compared with control strains. The depressor responses to intra-arterial bradykinin injections 1) were not different between Brown Norway and Brown Norway-Hannover rats, 2) were potentiated by intravenous ramipril (60 pug), and 3) were attenuated by intra-arterial infusion of the bradykinin antagonist B4146 (40 /ig/kg/min) to a similar extent in both strains. In renal hypertensive (two-kidney, one clip) Brown Norway rats, the blood pressure reductions to intravenous bolus injections of ramipril (100 /tg) were significantly reduced both in extent and duration when compared with hypertensive Brown Norway-Hannover and Wistar rats. Intra-arterial infusion of B4146 (40 /tg/kg/min) attenuated the depressor response to ramipril in Wistar and Brown Norway-Hannover rats but had no effect in Brown Norway rats. In contrast, all three groups showed similar depressor responses to intravenous infusions of the angiotensin H receptor antagonist saralasin. These responses were not influenced by the bradykinin antagonist. Our data support the hypothesis that kinins are important for the acute antihypertensive actions of converting enzyme inhibitors.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat We studied the concentration of vascular ldninogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212±4 mm Hg in the hypertensive rats (n=33) and 120±l mm Hg in the normotensive rats (n=32) (p<0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56±8 versus 77±15), it was highly significant in the abdominal aorta (63±13 versus 167±17, p<0.001) and tail artery (48±8 versus 197±31, p< 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183±16 versus 380±38, p<0.003), abdominal aorta (565+61 versus 1,093±74, p<0.001), and tail artery (532±112 versus 1,243 ± 135, p< 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213±56 versus 131±31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (l,803±221 versus 771 ±79, p<0.003). Total venous kininogenase activity was significantly higher in the hypertensive rats (vena cava, l,850±171 versus 998±149,p<0.01; tail vein, 4,261 ±261 versus 2,521±212, p<0.001). In conclusion, we found that in rats with one-kidney, one clip renovascular hypertension both active and total vascular kininogenase are decreased in the arteries and increased in the veins. These changes may contribute to the pathogenesis of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID

摘要:

The renal and systemic changes after stenosis of the left renal artery (n=S) or sham stenosis (n=6) in conscious dogs were studied sequentially over 25 days. Stenosis produced a prompt rise in arterial pressure, which was at all times due to reduced peripheral vascular conductance, with no increase in cardiac output despite initial evidence of mild fluid retention. The decrease in peripheral conductance was attributable to 1) the stenotic kidney (25% of the total and due to the mechanical effect of the stenosis itself), 2) the nonstenotic kidney (about 15% of the total and not caused by angiotensin II), and 3) the nonrenal vasculature (60%). The decrease in conductance in the nonrenal vasculature was due partly to angiotensin II, but there was also a gradually developing non-angiotensin II component Acute administration of captopril caused significantly greater changes in arterial pressure and peripheral conductance throughout the period of stenosis than before stenosis (and greater than in sham-stenosis dogs), indicating that angiotensin II was constricting the peripheral vasculature even when plasma renin levels were no longer elevated. In the stenotic kidneys, captopril produced a fall in renal vascular resistance, but renal blood flow did not rise because there was an approximately equal rise in the resistance of the stenosis. There was no evidence for a role for the autonomic nervous system in the hypertension, as ganglion blockade (pentolinium) had similar hemodynamic effects before and after stenosis. Thus, the hypertension was due at all times to reduced peripheral conductance, with the two kidneys responsible for 40% of this reduced conductance.

ISSN:0194-911X    

出版商:OVID    

年代:1990

数据来源: OVID