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Query: UMLS:C0085580 (
essential hypertension
)
14,686
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Brain renin-angiotensin system hyperactivity has been implicated in the development and maintenance of hypertension. We reported previously in the brain that
aminopeptidase A
and aminopeptidase N are involved in the metabolism of angiotensin II and angiotensin III, respectively. By using in vivo specific and selective
aminopeptidase A
and aminopeptidase N inhibitors, we showed that angiotensin III is one of the main effector peptides of the brain renin-angiotensin system, exerting a tonic stimulatory control more than blood pressure in hypertensive rats. Aminopeptidase A, the enzyme generating brain angiotensin III, thus represents a potential target for the treatment of hypertension. We demonstrated here the antihypertensive effects of RB150, a prodrug of the specific and selective
aminopeptidase A
inhibitor, EC33, in spontaneously hypertensive rats, a model of human
essential hypertension
. Oral administration of RB150 in conscious spontaneously hypertensive rats inhibited brain
aminopeptidase A
activity, demonstrating the central bioavailability of RB150 and its ability to generate EC33 into the brain. Oral RB150 treatment dose-dependently reduced blood pressure in spontaneously hypertensive rats with an ED(50) of 30 mg/kg, lasting for several hours. This decrease in blood pressure is partly attributed to a decrease in sympathetic tone, reducing vascular resistance. This treatment did not modify systemic renin-angiotensin system activity. Concomitant oral administration of RB150 with a systemic renin-angiotensin system blocker, enalapril, potentiated the RB150-induced blood pressure decrease achieved in <2 hours. Thus, RB150 may be the prototype of a new class of centrally active antihypertensive agents that might be used in combination with classic systemic renin-angiotensin system blockers to improve blood pressure control.
...
PMID:Central antihypertensive effects of orally active aminopeptidase A inhibitors in spontaneously hypertensive rats. 2271 Jun 44
Essential hypertension
is one of the major contributors to premature morbidity and mortality due to the incresased risk for coronary heart disease, stroke, renal disease, peripheral vascular disease and vascular dementia for both men and women. However, its basic causes remain unknown. In the present work we studied the activity of several proteolytic regulatory enzymes related to renin-angiotensin-system (RAS) (
aminopeptidase A
, APA; aminopeptidase N, APN; aminopeptidase B, APB; and insulin-regulated aminopeptidase, IRAP); with oxytocin regulation (oxytocinase); with the metabolism of GnRH and TRH (pyrrolidone carboxypeptidase, Pcp); and with enkephalins metabolism (enkephalindegrading activity, EDA), to elucidate their role in the mechanisms responsible of
essential hypertension
and to discuss the possible gender differences. Serum samples of 53 individuals with
essential hypertension
and 60 healthy volunteers were collected and used to assay enzyme activities, gonad hormones testosterone and estradiol, TSH and free thyroxin (fT4). Differences were observed in APA, APN, Pcp and EDA specific activities, and in serum gonad hormone levels between hypertensive and control groups. Only Pcp activity showed gender differences. Regarding the RAS, APA is reduced while APN is increased, suggesting increased levels of angiotensin II and a facilitation of the conversion of angiotensin III in angiotensin IV. Thus, the changes in several RAS-regulating specific activities and other enzyme activities involved in the neuroendocrine modulation of gonad and stress-related functions are related to
essential hypertension
with minor gender differences. Therefore, aminopeptidases constitute new elements for the knowledge of the causes of
essential hypertension
and an alternative as therapeutic targets against the illness.
...
PMID:Circulating aminopeptidase activities in men and women with essential hypertension. 2393 Dec 76
Obesity is assumed to be a major cause of human
essential hypertension
; however, the mechanisms responsible for weight-related increase in blood pressure (BP) are not fully understood. The prevalence of hypertension induced by obesity has grown over the years, and the role of the renin-angiotensin-aldosterone system (RAAS) in this process continues to be elucidated. In this scenario, the
ob/ob
mice are a genetic obesity model generally used for metabolic disorder studies. These mice are normotensive even though they present several metabolic conditions that predispose them to hypertension. Although the normotensive trait in these mice is associated with the poor activation of sympathetic nervous system by the lack of leptin, we demonstrated that
ob/ob
mice present massively increased
aminopeptidase A
(
APA
) activity in the circulation.
APA
enzyme metabolizes angiotensin (ANG) II into ANG III, a peptide associated with intrarenal angiotensin type 2 (AT
2
) receptor activation and induction of natriuresis. In these mice, we found increased ANG-III levels in the circulation, high AT
2
receptor expression in the kidney, and enhanced natriuresis. AT
2
receptor blocking and
APA
inhibition increased BP, suggesting the ANG III-AT
2
receptor axis as a complementary BP control mechanism. Circulating
APA
activity was significantly reduced by weight loss independently of leptin, indicating the role of fat tissue in
APA
production. Therefore, in this study we provide new data supporting the role of
APA
in BP control in
ob/ob
mouse strain. These findings improve our comprehension about obesity-related hypertension and suggest new tools for its treatment.
NEW & NOTEWORTHY
In this study, we reported an increased angiotensin III generation in the circulation of
ob/ob
mice caused by a high
aminopeptidase A
activity. These findings are associated with an increased natriuresis found in these mice and support the role of renin-angiotensin-aldosterone system as additional mechanism regulating blood pressure in this genetic obese strain.
...
PMID:High aminopeptidase A activity contributes to blood pressure control in
ob/ob
mice by AT
2
receptor-dependent mechanism. 2794 Sep 65
