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

Arterial plasma kinins and mean arterial pressure were measured in intact and bilaterally nephrectomized rats infused with vehicle or bradykinin to study the role of 1) angiotensin converting enzyme (ACE) and other peptidases and 2) the kidney (a kininase-rich organ) in the metabolism of kinins in vivo. Before the infusion, rats were pretreated with vehicle, enalaprilat (an ACE inhibitor), or a cocktail of kininase inhibitors containing 1) enalaprilat, 2) DL-2-mercaptomethyl-3-guanidinoethyl-thiopropanoic acid (MGTA), a carboxypeptidase N inhibitor, 3) phosphoramidon, a neutral endopeptidase 24.11 inhibitor, and 4) bestatin, an aminopeptidase B inhibitor. In the rats with vehicle (n = 8), the cocktail did not significantly increase endogenous kinins (from 31 +/- 6 to 41 +/- 9 pg/ml, p = 0.94). In the rats infused with bradykinin (peptidase substrate), plasma kinins increased threefold in the group pretreated with the vehicle, 21-fold in the enalaprilat group, and 22-fold in the cocktail group. These increases were doubled by nephrectomy but were not affected by ureteral ligation. In the groups pretreated with the cocktail or enalaprilat, the hypotensive effect of bradykinin was correlated with plasma kinin concentration (r = 0.75, p less than 0.001). After bradykinin infusion was stopped, plasma kinins decreased by half in 10-12 seconds in the rats pretreated with vehicle, enalaprilat, or cocktail. We concluded that ACE and the kidney are important to the metabolism of circulating kinins while carboxypeptidase N, neutral endopeptidase 24.11 and aminopeptidase B are not. We also concluded that other tissue peptidases, not affected by either the above inhibitors or nephrectomy, play an important role in kinin metabolism.
Hypertension 1989 Sep
PMID:Role of angiotensin converting enzyme and other peptidases in in vivo metabolism of kinins. 254 61

The effect of acute intracerebroventricular (i.c.v.) injections of angiotensin II and III (ANG II and ANG III; 0, 1, 10 and 100 pmol in 2 microliters artificial cerebrospinal fluid (CSF) on blood pressure and water consumption was investigated in Okamoto-Aoki spontaneously hypertensive rats (SHR), and Wistar-Kyoto (WKY) and Sprague-Dawley (SD) normotensive controls. Heightened sensitivity to i.c.v. ANG II and ANG III was observed in the SHR compared with the WKY and SD strains (P less than 0.001), for both pressor and drinking responses. In addition, i.c.v. treatment with an aminopeptidase B inhibitor, bestatin (20 nmol in 1 microliter artificial CSF) significantly potentiated the heightened pressor response to i.c.v.-injected ANG II and ANG III (100 pmol) in SHR and to a lesser degree in WKY animals compared with SD controls (P less than 0.001). These results suggest that a dysfunction in central aminopeptidase activity results in an extended life of endogenous angiotensins, and perhaps other peptides that may contribute to the high blood pressure seen in this animal model of human essential hypertension.
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PMID:Heightened pressor effect and dipsogenicity to intracerebroventricularly applied angiotensin II and III in spontaneously hypertensive rats. 347 26

We performed a longitudinal study for 20 weeks on spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKR) to determine the relationship between peptide metabolism and the age-dependent increase in blood pressure. In both SHR and WKR, the plasma level of aminopeptidase A (AP-A) clearly showed an age-dependent decrease. The plasma level of aminopeptidase B paralleled that of AP-A in WKR, but such an age-dependency was not observed in SHR, thus showing a dissociation between the two aminopeptidases. With age in both strains, the level of angiotensin-converting enzyme tended to decrease, while that of kallikrein activity tended to increase. In addition to these findings, a multivariate study testing the relationship of blood pressure to these enzyme activities, as well as to plasma levels of angiotensin I and renin activity, suggested abnormalities in the networks of proteolytic enzymes and in the peptide metabolism surrounding the renin-angiotensin system in SHR. These abnormalities may play some important roles in pathophysiological mechanisms of hypertension in SHR.
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PMID:The dissociation between the plasma levels of aminopeptidases A and B in spontaneously hypertensive rats. 354 51

Aminopeptidase A (APA)- and aminopeptidase M (APM)-like activity were assayed in Moni-Trol ES with L-alpha-aspartyl-beta-naphthylamide and L-alanyl-beta-naphthylamide, respectively. Upon preincubation of the serum with 89.4, 223.5, and 447 mM acetaldehyde at room temperature for 30 min, a reduction in 26.8%, 55.3%, and 75.8% aminopeptidase A activity was observed. Similarly, aminopeptidase M activity was reduced by 26.5% and 53.1% upon preincubation with 223.5 and 447 mM acetaldehyde. Ethanol at 84.9, 212.3, and 427.9 mM did not significantly affect the enzymic activity. Because aminopeptidase A and aminopeptidase M also degrade the pressor substance, angiotensin II, it is suggested that inhibition of aminopeptidase A- and aminopeptidase M-like activity by acetaldehyde, the product of ethanol metabolism, may lead to higher levels of circulating angiotensin II and, consequently, hypertension, in alcoholics. The hydrolysis of lysine-p-nitroanilide, an aminopeptidase B substrate, was also inhibited upon addition of acetaldehyde to Moni-Trol ES serum.
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PMID:Acetaldehyde inhibits serum aminopeptidases. 881 45

Aminopeptidase activity (AP) has been implicated in the metabolism of renal and circulating vasoactive peptides. This activity is involved in the pathogenia of hypertension, essentially in spontaneously hypertensive rats. However, no other animal models, which develop hypertension by other different ways, have been used to study the possible role of aminopeptidase activity. To investigate the role of this activity in the pathogenesis of hypertension, angiotensinase A activity (glutamyl-AP and aspartyl-AP), aminopeptidase M activity (alanyl-AP), aminopeptidase B activity (arginyl-AP), pyroglutamyl-AP, and cystinyl-AP were measured in the serum and kidney of two experimental animal models of renovascular hypertension: Goldblatt two-kidney one clip (G2K-1C) and low renal mass rats (LRM). No differences were found in serum levels of AP in LRM or G2K-1C in comparison with their respective controls. In LRM rats there was a significant decrease in membrane-bound angiotensinase A (glutamyl-AP), arginyl-AP and alanyl-AP activities. In G2K-1C rats there was a significant decrease in soluble and membrane-bound angiotensinase A activity (aspartyl-AP). Our results suggest that AP activities play a role in the regulation of renal vasoactive peptides, and respond differently depending on the cause of hypertension.
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PMID:Renal aminopeptidase activities in animal models of hypertension. 965 75

Aminopeptidase activity plays a role in the metabolism of several peptides that could be involved in blood pressure control. This activity has been implicated in the pathogenesis of hypertension, essentially in spontaneously hypertensive rats. However, few studies have examined aminopeptidase activities in animal models other than genetic hypertension. To analyze the aminopeptidase response to the specific conditions of the reduced renal mass saline model of arterial hypertension, aminopeptidase A activity (glutamyl- and aspartyl-aminopeptidase), aminopeptidase M activity (alanyl-aminopeptidase), aminopeptidase B activity (arginyl-aminopeptidase), pyroglutamyl-aminopeptidase and cystinyl-aminopeptidase were measured in the neurohypophysis, in the adrenal gland and in serum of this model of hypertension. In the neurohypophysis, there was a significant increase of soluble cystinyl-, alanyl-, arginyl-, pyroglutamyl- and membrane-bound aspartyl-aminopeptidase activities in hypertensive animals. In the adrenal gland, soluble cystinyl-, alanyl-, arginyl- and pyroglutamyl-aminopeptidase activities were also higher in hypertensive rats than in normotensive controls. No differences were found in serum levels of aminopeptidase activities between both groups of animals. A highly significant positive correlation between the neurohypophysis and the adrenal gland was observed for soluble cystinyl- and alanyl-aminopeptidase activities in the model of hypertension, whereas no correlation was observed in normotensive rats. Our results suggest that aminopeptidase activities could be involved in the regulatory response to the reduced renal mass hypertension and also suggest a coordinate response between the adrenal gland and the neurohypophysis, to the specific metabolic conditions of this model of hypertension.
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PMID:Activities of aminopeptidases in a rat saline model of volume hypertension. 966 82