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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular angiotensin converting enzyme could contribute to the elevated vascular resistance found in hypertension. The purpose of this study was to determine if angiotensin converting enzyme activity was present in the hindquarter vasculature of one model of hypertension, the spontaneously hypertensive rat (SHR) and its normotensive control, the Wistar-Kyoto rat (WKY). We evaluated the effect of a maximal blocking dose of captopril (0.5 mg) on the angiotensin I pressor response during the infusion of the hindquarter with an artificial perfusate. Angiotensin I (1000 ng/ml) produced a significant increase in peripheral vascular resistance (PVR) in both SHR and WKY, but the increase was greater in SHR. Captopril inhibited the elevation in PVR in both. A lower concentration of angiotensin I (250 ng/ml) produced a significant and similar pressor response in SHR (less than the pressor response to 1000 ng/ml) and WKY (same as the pressor response to 1000 ng/ml). Again, captopril prevented the elevation in PVR to A1 in both SHR and WKY. Because these studies were performed using an artificial perfusate, angiotensin converting enzyme must be present in the SHR and WKY hindquarter vasculature including resistance vessels.
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PMID:Evidence for a captopril-sensitive angiotensin converting enzyme in the hindquarter vasculature of SHR and WKY. 299 65

Plasma renin activity, plasma renin substrate (angiotensinogen), angiotensin I (AI), and plasma angiotensinase activity were measured in 8 women who had first become hypertensive during a mean 3.1 years on various oral contraceptives, and in 5 normotensive women, before and after 1 cycle of pills. All were determined by radioimmunoassay. 8 or more blood pressures were taken by 2 observers and averaged. Plasma renin activity increased from mean 2.12 to 3.52 ng/ml/hr (p greater than .2) in normal women, and from 3.0 to 5.06 in hypertensives (p less than .02). The mean plasma renin substrate values for both groups together rose from 1881 ng/ml to 4245 ng/ml. Angiotensin I rose from .029 ng/ml/hr to .049 in normals, and .027 to .037 in hypertensives. Mean plasma angiotensinase activity values rose from 3.6 to 5.4% degraded per minute in normal women and varied only from 6.5 before and to 5.9 after a pill cycle in hypertensive patients. The authors suggest that development of hypertension during oral contraceptive therapy may be due to abnormal inactivation of angiotensin.
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PMID:Effect of oral contraceptive therapy on the renin-angiotensin system in normotensive and hypertensive women. 434 64

The effects of angiotensin I (AT I), angiotensin II (AT II) and the activity of AT I converting enzyme (ACE) were investigated in isolated portal veins of normotensive rats (WKR and NCR) and of rats with primary (SHR) and secondary (one clip 2 kidney renal; RHR) hypertension. Based on ED50 values, the tissue sensitivity to AT II was slightly less in the portal veins of RHR than SHR, while the sensitivity of smooth muscle in NCR and WKR was similar to that of SHR. Angiotensin I induced contractions were inhibited by saralasin and by captopril, indicating presence of functionally active converting enzyme in the this vascular tissue. The local concentration of AT II formed from AT I, was evaluated based on AT II dose response curves and AT I response magnitude. The AT II formation was essentially similar in SHR, WKR and NCR and slightly enhanced in RHR. Inhibition of AT II formation with captopril and/or blockade of AT II receptors with saralasin failed to alter the spontaneous myogenic activity of the portal vein. Captopril reduced smooth muscle activity only in concentration several orders of magnitude greater than that needed to inhibit ACE. The concentration of captopril needed to inhibit AT I responses was similar in all strains of rats. It is concluded that AT II is rapidly formed in the portal vein due to local conversion of AT I. In the RHR portal vein the extent of AT I conversion is increased and the tissue sensitivity to AT II is decreased possibly due to mechanisms involved in the development of renovascular hypertension.
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PMID:Angiotensin I converting enzyme activity in portal vein studied in normotensive rats and in models of primary and secondary hypertension. 617 Nov 36

Rabbit aortic rings with either an intact endothelium or a disrupted endothelium were used to generate dose response curves to angiotensin I (AI) in the presence (ED50 = 3 X 10(-7) M) and absence (ED50 = 1.7 X 10(-8) M) of 10 micrograms/ml teprotide, a converting-enzyme inhibitor. Treatment with teprotide did not alter responses to angiotensin II (AII). Comparable dose-dependent responses were obtained with AII regardless of endothelial integrity. Contraction velocities in response to angiotensin I (10(-7) M) and AII (10(-7) M) were also measured. Angiotensin II produced a significantly greater contraction velocity (p less than 0.001) than that produced by AI. The amount of conversion to AII by both intact rabbit aortic rings and rings following removal of the endothelium was determined using 125I-AI and 125I-AII. Waters C18 SEP-PAK columns were used to separate AI and AII. During the first 3 to 4 minutes after the addition of AI, contraction velocity measurements and conversion were greater in intact rings than rings without endothelium. Conversion of AI to AII in endothelial-disrupted rings was the same as in intact rings by 5 minutes after the addition of AI. Conversion of AI to AII was inhibited by 30 micrograms/ml teprotide at all times measured, and there was no evidence of an alternate route of metabolism. Angiotensin I contraction velocity measurements after 10 micrograms/ml teprotide also demonstrated impaired efficiency of conversion of AI to AII. Thus, it was established that a lack of endothelium attenuated the rate of conversion of AI to AII initially, and formation of AII with or without endothelium was blocked by teprotide.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension
PMID:Role of endothelium in conversion of angiotensin I to angiotensin II in rabbit aorta. 620 32

Angiotensin-converting enzyme (ACE) was studied in preparations of microvessels isolated from rabbit cerebral cortex. Activity was determined by measuring the degradation of hippuryl-histidyl-leucine (Hip-His-Leu) by the intact microvessels in a physiological salt solution at pH 7.4. ACE activity was dependent on both substrate and chloride ion concentration and was inhibited by captopril in a manner similar to that observed previously with tissue homogenates. Angiotensin I was rapidly degraded by the intact microvessels, even in the presence of 10(-6)M captopril. An advantage of the methodology employed was the ability to pretreat the microvessels and then assess the effect of pretreatment by transfer to a postincubation assay system. Pretreatment with a hyperosmolar urea solution did not change ACE activity or cause release of ACE from the microvessels, although lactic dehydrogenase and lysosomal enzymes were released. Pretreatment with captopril caused a lag in the subsequent degradation of Hip-His-Leu, presumably reflecting dissociation of inhibitor from the cell-associated enzyme. ACE activity was unaffected by hypoxic or anoxic incubation conditions. The ability to measure ACE activity of the microvessels in vitro provides a unique opportunity to study the properties of the enzyme in intact cerebrovascular endothelial cells.
Hypertension
PMID:Properties of angiotensin-converting enzyme in intact cerebral microvessels. 626 Jun 46

The aim of this study was to develop a method for the measurement of renin activity in small tissue samples obtained from rat brains by the micropunch technique and to investigate the activity of brain renin in spontaneously hypertensive rats. The assay satisfied sensitive and specificity requirements. Angiotensin I was generated at a pH of 6.0; complete recovery of angiotensin I and kinetic studies supported the specificity of the method. Angiotensinase and cathepsin D-like acid protease activity were measured in parallel with renin. Renin was present in all brain regions studied and decreased with the age of the animals. An increased activity of renin was measured in several nuclei of the brain stem and in the neurohypophysis of young hypertensive rats when compared with age-matched normotensive control animals. These differences disappeared in older rats. There was a dissociation between renin and cathepsin D-like acid protease activity. No correlation existed between the distribution of renin and angiotensinase activity. The increased renin activity in brain stem nuclei of spontaneously hypertensive animals is in agreement with previous findings that the brain renin-angiotensin system contributes to the maintenance of high blood pressure in these rats.
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PMID:A micromethod for the measurement of renin in brain nuclei: its application in spontaneously hypertensive rats. 628 32

From the in vitro and in vivo measurements of the components of the renin-angiotensin system (RAS) in the cerebrospinal fluid (CSF) of rats and dogs, it was concluded that angiotension II (ANG II) is not generated within the CSF in significant amounts, since renin was found to be unmeasurable in CSF under most circumstances. The specific concentrations of angiotensinogen and of converting enzyme (CE) were high. Angiotensin I (ANG I) concentrations were low in CSF, while ANG II levels were comparable to those measured in plasma under control conditions. Neither ANG I nor ANG II penetrated from the blood into the brain ventricles of rats, provided that no unrealistically high doses of ANG II were administered intravenously. This holds true even if high blood pressure increases were induced by intravenous ANG II infusion in deoxycorticosterone acetate (DOCA) and salt-treated rats. However, increased ANG II concentrations were measured in CSF perfusate, when the blood-brain barrier (BBB) was opened by the intracarotid injection of a hyperosmolar urea solution. The brain ventricular perfusion of increasing concentrations of ANG II revealed constant recovery of less than 40%. CSF did not contain angiotensinase activity, but ANG II degradation was high in some periventricular regions. ANG II, the ANG II antagonist saralasin, and the CE inhibitor captopril, respectively, escaped from CSF into circulation when high doses of these substances were applied intraventricularly. We conclude that ANG II in the CSF does not originate from and is not related to plasma ANG II. It is probably not generated within the CSF. ANG II may be synthetized in the brain tissue and be released into the brain ventricles where its rapid degradation occurs in contact with circumventricular structures.
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PMID:Components of the renin-angiotensin system in the cerebrospinal fluid of rats and dogs with special consideration of the origin and the fate of angiotensin II. 700 24

Angiotensin I (Ang I), Ang II, angiotensinogen, and renin are formed locally in the vasculature. We undertook this study to determine whether the rat mesenteric artery produces aldosterone and to investigate the effects of adrenalectomy, an angiotensin-converting enzyme inhibitor, Ang II, or potassium on aldosterone production in vascular tissue. Isolated rat mesenteric arteries were perfused with Krebs-Ringer solution for 4 hours. The perfusate was collected and chromatographed in a reversed-phase high-performance liquid chromatographic (HPLC) system. The fraction corresponding to synthetic aldosterone was collected and analyzed by mass spectrometry. The aldosterone concentration in the perfusate from the adrenalectomized rats and rats treated with an angiotensin-converting enzyme inhibitor was measured using radioimmunoassay after HPLC separation. The mass spectra of synthetic aldosterone and aldosterone isolated from the perfusate of rat mesenteric arteries were identical. Aldosterone production in the mesenteric arteries of adrenalectomized rats was increased and of rats treated with an angiotensin-converting enzyme inhibitor was reduced compared with that of controls. Ang II (1.9 x 10(10) mol/L) and potassium (6.0 mmol/L) increased aldosterone production in mesenteric arteries. This study shows that the rat mesenteric artery produces aldosterone and that the intravascular renin-angiotensin-aldosterone system may contribute to vascular tone.
Hypertension 1995 Feb
PMID:Production of aldosterone in isolated rat blood vessels. 784 66

Angiotensin I-converting enzyme (ACE) is known to be present at the surface of endothelial cells and also in the adventitia in large vessels. The presence of ACE in the vascular smooth muscle remains controversial. We microdissected segments of adventitia and media with or without endothelium from a region devoid of collateral arteries. The membrane-bound ACE activity in the media averaged 41% (pmol [glycine-1-14C]hippuryl-L-histidyl-L-leucine hydrolyzed.g tissue-1.min-1) of the values found in the whole aorta, whereas the adventitia contained only 6%. Immunoreactive ACE in media was characterized by Western blotting. ACE mRNAs were detected and characterized after polymerase chain amplification in isolated media. Angiotensin I and angiotensin II were equally able to contract medial rings, and the response to angiotensin I was blocked by enalaprilat. In aortas of two-kidney, one-clip hypertensive rats, there was an increase in ACE mRNA estimated by ribonuclease protection assay (P = 0.02) and in ACE activity at 15 days and 1 and 3 mo after clipping. This corresponded to a 1.5- to 2-fold increase in the ACE activity of both the media and the adventitia compared with sham-operated rats (P < or = 0.02). Thus ACE gene expression occurs in smooth muscle of rat aorta, which contains roughly the same amount of enzyme as the endothelium and readily converts angiotensin I to angiotensin II. ACE in the medial layer and the adventitia is upregulated in renovascular hypertension.
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PMID:ACE in three tunicae of rat aorta: expression in smooth muscle and effect of renovascular hypertension. 797 8

The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of renin-angiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)-generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site-directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n = 11) and Ang I (n = 7) and II (n = 7) in the left and right atria were higher than in the corresponding ventricles (P < .05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P < .05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n = 11) in cardiac tissue were 10% to 25% of the levels in plasma, which is compatible with its diffusion from plasma into the interstitium. Like angiotensin-converting enzyme, renin was enriched in a purified cardiac membrane fraction prepared from left ventricular tissue, as compared with crude homogenate, and 12 +/- 3% (mean +/- SD, n = 6) of renin in crude homogenate was found in the cardiac membrane fraction and could be solubilized with 1% Triton X-100. Tissue levels of renin and Ang I and II in the atria and ventricles were directly correlated with plasma levels (P < .05), and in both tissue and plasma the levels were undetectably low after nephrectomy. We conclude that most if not all renin in cardiac tissue originates from the kidney. Results support the contentions that in the healthy heart, angiotensin production depends on plasma-derived renin and that plasma-derived angiotensinogen in the interstitial fluid is a potential source of cardiac angiotensins. Binding of renin to cardiac membranes may be part of a mechanism by which renin is taken up from plasma.
Hypertension 1994 Jul
PMID:Cardiac renin and angiotensins. Uptake from plasma versus in situ synthesis. 799 42


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