Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypotensive effects of N-[8-amino-1(S)-carboxyoctyl] -L-alanyl-L-proline (AB-47, CAS 120008-53-9) were examined in normotensive rats and various hypertensive rat models. The hemodynamic effect of AB-47 was also examined in anesthetized spontaneously hypertensive rats (SHR). In 2-kidney, 1-clip renal hypertensive rats (2K, 1C-RHR) and SHR, the single administration of AB-47 (10 mg/kg, p.o.) induced potent and long-lasting hypotensive effects. The repeated administration of AB-47 (1 to 10 mg/kg, p.o.) to SHR for 29 days produced a dose-dependently and sustained hypotensive effect of 20 to 70 mmHg. AB-47 (10 mg/kg, p.o.) had a weak hypotensive effect in DOCA-salt hypertensive rats but no effects in normotensive and 1-kidney, 1-clip renal hypertensive rats (1K, 1C-RHR). AB-47 (3 mg/kg, p.o.) reduced blood pressure in intact SHR but not in bilateral nephrectomized SHR. The single intravenous injection of AB-47 (10 to 100 micrograms/kg) dose-dependently lowered systemic blood pressure, left ventricular systolic pressure (LVSP) and dp/dtmax without affecting heart rate (HR) and these effects of AB-47 were more potent than those of captopril and enalaprilat. These results suggest that AB-47 is a potent and long-lasting hypotensive agent and may be useful for the therapy of both hypertension and congestive heart failure.
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PMID:Hypotensive and hemodynamic effects of the new non-sulfhydryl angiotensin converting enzyme inhibitor N-[8-amino-1(S)-carboxyoctyl]-L-alanyl-L-proline. 209 26

The properties of [3H]nitrendipine binding to cardiac and cerebral membranes from normotensive Wistar-Kyoto (WKY) and renal (RHR), deoxycorticosterone/NaCl (DOCA-HR) and spontaneously hypertensive (SHR) rats were investigated. The maximal numbers of binding sites (Bmax) in the striatum, thalamus and hippocampus for SHR increased by 21.4-40.0, 28.1-40.4 and 21.4-34.1% of the numbers in WKY, but the apparent dissociation constants (KD) in the cerebral membranes differed very little between WKY and SHR. In the cardiac membranes, KD and Bmax values differed very little between WKY and SHR. In the RHR and DOCA-HR, the Bmax values in the striatum, thalamus and hippocampus were similar to those of WKY. These findings suggest that the increase in Bmax of [3H]nitrendipine in the striatum, thalamus and hippocampus of SHR may play a part in the development and maintenance of high blood pressure in SHR.
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PMID:Binding of [3H]nitrendipine to cardiac and cerebral membranes from normotensive and renal, deoxycorticosterone/NaCl and spontaneously hypertensive rats. 294 Jan 2

Exercise is known to promote myocardial vascularity. We therefore studied whether it could prevent coronary abnormalities of hypertensive left ventricular (LV) hypertrophy. Female Sprague-Dawley 1 clip-2 kidneys Goldblatt hypertensive rats (RHR) and their appropriate controls (Sham-SH), were either made to swim (RHR-SW, SH-SW) or kept sedentary (RHR-SED, SH-SED) for 9 weeks. Maximal coronary blood flow (LV CBF, ml/min/gm) and minimal coronary resistance after carbochrome (total LVCR/LV mmHg/ml/min), an index of the functional cross sectional area (CSA) of coronary resistance vessels, were determined in conscious rats by microspheres. Results (m +/- SD) (n = 12 in all groups): (Table: see text). Exercise increased functional coronary CSA in normotensive rats only. This beneficial effect did not occur in hypertension, probably because of functional changes in the coronary vessels of RHR.
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PMID:[Effects of exercise on coronary circulation in left ventricular hypertrophy caused by hypertension]. 294 70

Left ventricular hypertrophy can be reversed by treatment of hypertension with captopril but the consequences of this regression are not yet fully described. We studied the maximal capacity of the hypertrophied and hypertrophy-reversed ventricle to generate pressure during transient total occlusion of the aorta, and also the left ventricular end-diastolic pressure required to meet this maximal effort. Two-kidney, one clip Goldblatt (renal hypertensive rats; RHR) hypertension was induced in 17 Wistar rats, eight of which were treated with captopril (RHR-C: 50 mg/kg given orally) from the fourth to the eighth week. Sham-operated controls (SC) remained untreated, or were treated with similar doses of captopril (SC-C). Significantly lower heart weights were found in RHR-C than in RHR (2.88 +/- 0.15 versus 2.38 +/- 0.04; P less than 0.001). During transient total occlusion of the aorta, the maximal intraventricular pressure developed in RHR-C was not significantly different from that in RHR, but left ventricular end-diastolic pressure was significantly less in RHR-C than in RHR (21.4 +/- 2.2 versus 34.3 +/- 3.8; P less than 0.01). The analysis of pressure-volume characteristics of the hypertrophied left ventricles and those in which hypertrophy was reversed revealed similar compliances between these two groups. Our data suggest that there was a mechanical improvement in the heart function after reversal of left ventricular hypertrophy.
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PMID:Consequences of reversal of hypertensive cardiac hypertrophy by captopril on left ventricular pumping ability and performance. 296 26

This study investigate the effects of Nicardipine treatment on regression of left ventricular hypertrophy (LVH), coronary hemodynamic and myocardial mechanical performance. 30 Sprague-Dawley male rats were divided into 3 groups: sham operated rats control group (SHC), untreated hypertensive rats group (RHR-U), treated hypertensive rats group (RHR-N). Systemic and coronary hemodynamics were determined by using left atrial injection of radioactive microspheres, 16 weeks after clipping. Mechanical performance was measured on isolated papillary muscle from the same animal. Results (mean +/- SEM) (Table: see text). Nicardipine treatment (10 to 15 mg intraperitoneal dosage during 8 weeks), led to: an efficient but incomplete control of hypertension. a reduction of left ventricular mass in proportion lesser than pressure decrease. a raise of coronary blood flow at rest with inversion of flow distribution between endocardium an epicardium. a decrease of "maximal" coronary blood flow. a reversal of impaired myocardial mechanical parameters towards control values except for contraction timing parameters. Decrease of "maximal" coronary blood flow could have deleterious effects on cardiac function.
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PMID:[Effects of nicardipine on left ventricular hypertrophy of the rat with renovascular arterial hypertension]. 297 1

The hypertrophied myocardium of 2 kidney-1 clip renal hypertensive rats (2K-1C RHR) displays reduced responsiveness to phenylephrine stimulation. We have studied the effects of hypertrophy on alpha 1-receptor binding properties in three models of hypertension. Specific binding density of an alpha 1-selective antagonist [3H]-prazosin to ventricular membrane of 6 and 10 weeks 2K-1C RHR was significantly decreased (45 +/- 9 fmol/mg protein, n = 14, vs 64 +/- 7.8 fmol/mg protein, n = 20, p less than .001) compared to age matched sham operated control group, but with no change in the total alpha 1-receptor content in the hypertrophied ventricles. The 4 week 1K-1C RHR showed a 29% decrease in alpha 1-adrenergic receptor density with no change in affinity. In contrast, the spontaneously hypertensive rats (SHR) showed an increase in alpha 1-receptors in the prehypertensive stage (4 weeks old) (115.2 +/- 4.9 fmol/mg protein, n = 10, vs 88.7 +/- 12 fmol/mg protein, n = 10, p less than .001) and in the adult stage with established hypertension (15 weeks old) (87.1 +/- 10.5 fmol/mg protein, n = 10, vs 67.3 +/- 9 fmol/mg protein, n = 10, p less than .001) compared to age matched or heart weight matched Wistar Kyoto rats (WKY). Reduced responsiveness to phenylephrine in RHR may be due to reduced density of alpha 1-receptors, but the reason for the increase in alpha 1-receptors in SHR's myocardium remains unclear.
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PMID:Alterations of myocardial alpha 1-adrenergic receptors in hypertensive cardiac hypertrophy in the rat. 302 69

Inotropic responses to isoproterenol of hypertrophied hearts have been shown to be decreased. We have previously reported that in 13-week-old spontaneously hypertensive rats (SHR) this decrease is probably due to decreased beta-adrenergic receptor number, while in hearts from two kidney-one clip renal hypertensive rats (2K-1C RHR), this is due to a decreased nucleotide regulatory protein activity. We now show that changes in 2K-1C RHR are time dependent. One week after instituting development of hypertension the heart is already hypertrophied. Biochemical changes consistent with decreased glucagon receptors are seen, as well as beginning changes consistent with decreases in the nucleotide regulatory protein activity. By two weeks this is more evident. Hypertrophy and biochemical changes can be reversed up to six weeks, but by ten weeks the activity of the catalytic subunit of the adenylate cyclase system is decreased. In 1K-1C RHR, biochemical changes in the cyclase system are accelerated as compared with the 2K-1C model. In SHR, changes in 24-week-old rats are the same as in the 13-week-old rats. It is concluded that in cardiac hypertrophy associated with different models of hypertension the decreased inotropic responsiveness to isoproterenol is associated with different biochemical defects in the beta-adrenergic receptor response coupling pathway, and that reversal in function occurs only when there is no apparent change in the catalytic subunit of the adenylate cyclase complex.
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PMID:Adenylate cyclase activity during development and reversal of cardiac hypertrophy. 316 Aug 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

Performance of the hypertrophied left ventricle was studied by determination of the inotropic response to different stimuli in renal hypertensive rats (two-kidney, one clip Goldblatt, RHR, n = 13) and matched sham-operated controls (NR, n = 11). A model was developed to determine maximal pressure development (transient aortic ligation), maximal pumping ability (rapid transfusion, 2 ml/30 sec), and responses to beta stimulation (isoproterenol, 0.01 to 0.10 micron g/kg/min), using dP/dt/P40 as a load-independent index of contractility. With rapid blood transfusion, RHR developed a higher ventricular systolic pressure (211.5 +/- 10.1 mm Hg vs 194.0 +/- 9.3 (SE), p less than 0.001) but at the expense of higher end-diastolic pressure (LVEDP) (12.2 +/- 1.1 mm Hg vs 7.7 +/- 1.0, p less than 0.02). The maximal response of dP/dt/P40 to isoproterenol was diminished in RHR (29.5 +/- 3.2 sec-1 vs 49.6 +/- 5.2, p less than 0.01) whereas the maximal developed pressure (MDP) was greater in RHR than in NR (239.2 +/- 7.5 mm Hg vs 197.0 +/- 3.9, p les than 0.001). A positive correlation was found between MDP and ventricular weight (r = 0.846, p less than 0.001) in contrast with the negative correlation found between ventricular weight and maximal dP/dt/P40 response to isoproterenol (r = 0.677, p less than 0.001). Thus, cardiac hypertrophy in RHR allowed higher developed ventricular pressures but at the expense of higher LVEDP; at the same time, however, the ability to increase contractility in response to beta adrenergic stimulation was decreased. The contrast in results obtained using different tests of cardiac function indicates the need for a multifactorial approach. It also suggests a subtle transformation in this hypertrophy of the pattern of cardiac adaptation to the increased load.
Hypertension
PMID:Left ventricular hypertrophy in rats with renovascular hypertension. Alterations in cardiac function and adrenergic responses. 627 70

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.
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PMID:Effect of DOCA-salt on angiotensin dependency and surgical reversal of hypertension in two-kidney, one clip renal hypertensive rats. 639 14


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