Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neuropeptide Y (NPY) is a co-transmitter of the sympathetic nervous system including the renal nerves. The kidney expresses NPY receptors, which can also be activated by peptide YY (PYY), a circulating hormone released from gastrointestinal cells. Five subtypes of NPY receptors have been cloned, among which Y1, Y2 and Y5 appear to be involved in the regulation of renal function. NPY produces potent renal vasoconstriction in vitro in isolated interlobar arteries and in the isolated perfused kidney and in vivo upon intrarenal or systemic administration via a Y1 receptor. Nevertheless glomerular filtration rate is altered only little if at all by NPY, indicating a greater effect on the vas efferens than the vas afferens. NPY can inhibit renin release via Y1-like receptors. NPY can stimulate Na+/K+ adenosine triphosphatase (Na+/K+-ATPase) in proximal tubules via Y2 receptors and can antagonize the effects of vasopressin on isolated collecting ducts. It can also act prejunctionally to inhibit noradrenaline release via Y2 receptors. Despite the profound reductions of renal blood flow, systemic NPY infusion can cause diuresis and natriuresis; this is largely independent of pressure natriuresis mechanisms and is possibly mediated by an extrarenal Y5 receptor. Studies with the converting enzyme inhibitor ramiprilat and the bradykinin receptor antagonist icatibant indicate that bradykinin mediates, at least partly, diuretic NPY effects. NPY antagonists enhance basal renal blood flow but do not alter basal diuresis or natriuresis indicating that renovascular, but not tubular, NPY receptors may be tonically activated by endogenous NPY.
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PMID:Renal effects of neuropeptide Y. 944 90

Inhibition of the renin-angiotensin system has been shown to improve symptoms and prognosis in heart failure. We compared the effects of inhibition of angiotensin-converting enzyme or blockade of angiotensin II type 1 (AT1) receptors in a model with renin-induced hypertension that is known to exhibit similar changes in sympathetic activation and beta-adrenergic desensitization, as observed in heart failure. Treatment with captopril (100 mg/kg of feed) or the AT1-antagonist Bay 10-6734 (100 mg/kg of feed) was performed in transgenic rats harboring the mouse renin 2d gene [TG(mREN2)27]. Neuropeptide Y and angiotensin II levels, adenylyl cyclase activity, beta-adrenergic receptors, G(salpha), and G(ialpha) were investigated. TG(mREN2)27 showed a depletion of myocardial neuropeptide Y stores and an increase in myocardial angiotensin II concentrations. Isoprenaline- and guanylylimidodiphosphate-stimulated adenylyl cyclase activities and beta-adrenergic receptor density were reduced, whereas the catalyst and G(salpha)-function were unchanged. G(ialpha) protein and mRNA concentrations were increased. All alterations were normalized by both treatments. Systolic left ventricular pressures, plasma atrial natriuretic peptide, and myocardial steady state atrial natriuretic peptide mRNA concentrations and heart weights were similarly reduced by both treatments. Sympathetic neuroeffector defects are similarly reversed by angiotensin-converting enzyme inhibition or AT1 antagonism. The data support the concept that pharmacological interventions in the myocardial renin-angiotensin system significantly reverse local sympathetic neuroeffector defects. This could be important for the beneficial effects of these agents.
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PMID:Effects of angiotensin II type 1 receptor blockade and angiotensin-converting enzyme inhibition on cardiac beta-adrenergic signal transduction. 949 57

Hypertension often occurs with fluid overload. The most common mechanism is considered to be mediated by increased cardiac output. Hemodialysis (HD) patients frequently have large amounts of fluid overload. Neuropeptide Y (NPY) is activated by stress and contributes to hypertension and heart failure. We speculated that NPY may be released by the stress of fluid overload and, by its vasoconstrictor effect, may contribute to hypertension and heart failure. Plasma levels of NPY and other vasoconstrictors were studied in 20 HD patients with varying degrees of fluid overload, and the relationship of NPY plasma levels to blood pressure was analyzed. The plasma concentrations of NPY correlated with the degree of fluid overload (r = 0.89; P < 0.0001) and the mean arterial blood pressure (r = 0.85; P < 0.0001). Seven patients had fluid overload of greater than 6% of body weight. They had higher blood pressures and higher plasma concentrations of NPY than 13 HD patients with less than 5% of fluid retention (systolic blood pressure, 179+/-8.2 v 145+/-3.7 mm Hg, P = 0.007; NPY, 61+/-4.6 v 26.8+/-2.7 pmol/L, P < 0.001). In stepwise multiple regression analysis, NPY alone explained blood pressure elevation when analyzed with fluid overload and angiotensin II, renin, noradrenaline, and adrenaline levels. We hypothesized that fluid overload in dialysis patients is a stress-inducing state that activates the sympathetic nervous system and releases the vasoconstrictor NPY. The resulting inappropriate vasoconstriction may contribute to volume-induced hypertension and heart failure in a vicious cycle. We conclude that determination of plasma NPY levels may be useful as a marker of the clinical threat of overhydration.
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PMID:Is neuropeptide Y a contributor to volume-induced hypertension? 959 Jan 90

Neuropeptide Y (NPY) is a key modulator of the autonomic nervous system playing pivotal roles in cardiovascular and neuronal functions. In this study, we assessed the cellular localization and gene expression of NPY in rat kidneys. We also examined the relationship between NPY gene expression and renin in two rat models of hypertension (two-kidney, one-clip renal hypertension (2K1C), and deoxycorticosterone-salt-induced hypertension (DOCA-salt)) characterized by a similar blood pressure elevation. In situ hybridization and immunohistochemistry, using anti-NPY or anti-C-flanking peptide of NPY (CPON) antibodies, showed that NPY transcript and protein were colocalized in the tubules of rat kidneys. During experimental hypertension, NPY mRNA was decreased in both kidneys of the 2K1C animals, but not in the kidney of DOCA-salt rats. In 2K1C rats, renal NPY content was also decreased. The difference in NPY gene expression between 2K1C rats (a high renin model of hypertension) and DOCA-salt rats (a low renin model of hypertension) suggests that circulating angiotensin II plays a role in local renal NPY gene expression and that the elevated blood pressure per se is not the primary factor responsible for the control of NPY gene expression in the kidney.
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PMID:Cellular localization, expression and regulation of neuropeptide Y in kidneys of hypertensive rats. 1045 44

Substance P inhibits renin secretion. This polypeptide is a transmitter in primary afferent neurons and is released from the peripheral as well as the central portions of these neurons. It is present in afferent nerves from the kidneys. Neuropeptide Y, which is a cotransmitter with norepinephrine and epinephrine, is found in sympathetic neurons that are closely associated with and presumably innervate the juxtagolmerular cells. Its effect on renin secretion is unknown, but it produces renal vasoconstriction and natriuresis. Vasoactive intestinal polypeptide (VIP) is a cotransmitter with acetylocholine in cholinergic neurons, and this polypeptide stimulates renin secretion. We cannot find any evidence for its occurence in neurons in the kidneys, but various stimuli increase plasma VIP to levels comparable to those produced by doses of exogenous VIP which stimulated renin secretion. Neostigmine increases plasma VIP and plasma renin activity, and the VIP appears to be responsible for the increase in renin secretion, since the increase is not blocked by renal denervation or propranolol. Stimulation of various areas in the brain produces sympathetically mediated increases in plasma renin activity associated with increases in blood pressure. However, there is pharmacological evidence that the renin response can be separated from the blood pressure response. In anaesthetized dogs, drugs that increase central serotonergic discharge increase renin secretion without increasing blood pressure. In rats, activation of sertonergic neurons in the dorsal raphe nucleus increases renin secretion by a pathway that projects from this nucleus to the ventral hypothalamus, and from there to the kidneys via the sympathetic nervous system. The serotonin releasing drug parachloramphetamine also increases plasma VIP, but VIP does not appear to be the primary mediator of the renin response. There is preliminary evidence that the serotonergic neurons in the dorsal raphe nucleus are part of the pathway by which psychosocial stimuli increase renin secretion.
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PMID:Peptides and neurotransmitters that affect renin secretion. 1154 Aug 33

Neuropeptide Y (NPY) is a cotransmitter with norepinephrine (NE) and ATP in sympathetic nerves. There is evidence for increased activity of the sympathetic nervous system and the renin-angiotensin system (RAS), as well as a role for NPY in the development of hypertension in experimental animal models and in humans. Angiotensin II (ANG II) is known to facilitate sympathetic neurotransmission, an effect greater in spontaneously hypertensive rats (SHR) than normotensive Wistar-Kyoto (WKY) rats. A newly discovered product of the RAS is angiotensin-(1-7) [ANG-(1-7)]. There is evidence suggesting that ANG-(1-7) opposes the actions of ANG II, resulting in hypotensive effects. The objective of this study was to investigate the role of ANG-(1-7) on the nerve-stimulated overflow of NE and NPY from the mesenteric arterial bed of SHR and the mechanisms involved in mediating any effects produced. ANG-(1-7) (0.001, 0.01, 0.1 microM) decreased nerve-stimulated NE and NPY overflow, as well as perfusion pressure in preparations obtained from SHR. This effect was greater in preparations of SHR than WKY controls. In addition, ANG-(1-7) decreased NE overflow to a greater extent than NPY overflow. Administration of the Mas receptor antagonist, D-Ala(7) ANG-(1-7), attenuated the decrease in both NE and NPY overflow due to ANG-(1-7) administration. However, the angiotensin type 2 receptor antagonist, PD-123391, attenuated the effect of ANG-(1-7) on NE overflow without affecting the decrease in NPY overflow. Moreover, in the presence of N(G)-nitro-L-arginine methyl ester, ANG-(1-7) decreased NPY overflow, but not NE overflow. ANG-(1-7) decreases the nerve-stimulated overflow of NE and NPY in preparations of SHR, whereas ANG II enhances it. Therefore, ANG-(1-7) may counteract the effects of ANG II by acting on ANG type 2 and Mas receptors.
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PMID:Inhibitory effects of angiotensin-(1-7) on the nerve stimulation-induced release of norepinephrine and neuropeptide Y from the mesenteric arterial bed. 1993 20


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