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

Considerable attention has been focused on the purine nucleoside, adenosine, in the control of renal blood flow, epithelial transport, and renin secretion; however, surprisingly little attention has been directed toward the renal effects of purine nucleotides such as adenosine triphosphate (ATP). Recent studies utilizing in vivo micropuncture and in vitro techniques have demonstrated that renal vascular, epithelial, and mesangial cells respond to extracellular ATP via mechanisms distinct from those elicited by adenosine. ATP vasoconstricts afferent but not efferent arterioles whereas adenosine vasoconstricts both vascular segments. Adenosine-mediated afferent arteriolar vasoconstriction is abolished by adenosine receptor antagonists, whereas the response to ATP is enhanced. ATP-mediated vasoconstriction reaches a maximum within seconds of exposure while the vasoconstriction induced by adenosine develops more slowly. L-type calcium channel antagonists such as diltiazem or felodipine prevent the sustained afferent vasoconstriction produced by ATP. Data from micropuncture experiments indicate that peritubular capillary infusion of ATP reduces glomerular pressure and results in marked attenuation of the tubuloglomerular feedback mechanism, which transmits signals from the macula densa to the afferent arteriole. These data support the existence of ATP-sensitive P2 purinoceptors in the preglomerular microvasculature that contribute to the control of renal vascular function via activation of calcium channels.
 ...
PMID:Extracellular ATP in the regulation of renal microvascular function. 814 38

Natriuretic peptides are cyclized peptides produced by cardiovascular and neural tissues. These peptides inhibit various secretory responses such as the release of renin, aldosterone and autonomic neurotransmitters. This report tests the hypothesis that atrial natriuretic peptide reduces dopamine efflux from an adrenergic cell line, rat pheochromocytoma cells, by suppressing intracellular calcium concentrations. The L-type calcium channel inhibitor, nifedipine, markedly suppressed dopamine release from depolarized PC12 cells, suggesting that calcium entering through this channel was the predominant stimulus for dopamine efflux. Atrial natriuretic peptide maximally reduced depolarization-evoked dopamine release 20 +/- 3% at a concentration of 100 nM and this effect was abolished by nifedipine, but not by pretreatment with the N-type calcium channel inhibitor, omega-conotoxin, or an inhibitor of calcium-induced calcium release, ryanodine. In cells loaded with Fura-2, atrial natriuretic peptide both augmented depolarization-induced increases of intracellular free calcium concentrations and accelerated the depolarization-induced quenching of the Fura-2 signal by manganese, findings consistent with enhanced conductivity of calcium channels. Dopamine efflux induced by either the calcium ionophore, A23187, or staphylococcal alpha toxin was attenuated by atrial natriuretic peptide. Additionally, a natriuretic peptide interacting solely with the natriuretic peptide C receptor in these cells, C-type natriuretic peptide, also suppressed calcium-induced dopamine efflux in permeabilized cells. These data are consistent with natriuretic peptides attenuating catecholamine exocytosis in response to calcium but inconsistent with the neuromodulatory effect resulting from a reduction in intracellular calcium concentrations within pheochromocytoma cells.
 ...
PMID:Atrial natriuretic peptide inhibits evoked catecholamine release by altering sensitivity to calcium. 935 54

1. This study aimed to investigate and to compare the effects of pharmacological T-type calcium channel and of L-type calcium channel blockade on the renin system. To this end, male healthy Sprague-Dawley rats were treated with the T-channel blocker mibefradil or with the L-channel blocker amlodipine at doses of 5 mg kg(-1), 15 mg kg(-1) and 45 mg kg(-1) per day for four days and their effects on plasma renin activity (PRA) and kidney renin mRNA levels were determined. 2. Whilst amlodipine lowered basal systolic blood pressure at 5 mg kg(-1), mibefradil had no effect on basal blood pressure in the whole dose range examined. Amlodipine dose-dependently induced up to 7 fold elevation of PRA and renin mRNA levels. Mibefradil significantly lowered PRA and renin mRNA levels at 5 mg kg(-1) and moderately increased both parameters at a dose of 45 mg kg(-1), when PRA and renin mRNA levels were increased by 100% and 30%, respectively. In primary cultures of renal juxtaglomerular cells neither amlodipine nor mibefradil (0.1-10 microM) changed renin secretion. 3. In rats unilateral renal artery clips (2K-1C) mibefradil and amlodipine at doses of 15 mg kg(-1) day(-1) were equally effective in lowering blood pressure. In contrast mibefradil (5 mg kg(-1) and 15 mg kg(-1) day(-1)) significantly attenuated the rise of PRA and renin mRNA levels, whilst amlodipine (15 mg kg(-1)) additionally elevated the rise of PRA and renin mRNA levels in response to renal artery clipping. 4. These findings suggest that T-type calcium channel blockers can inhibit renin secretion and renin gene expression in vivo, whilst L-type calcium channel blockers act as stimulators of the renin system. Since the inhibitory effect of T-type antagonists is apparent in vivo but not in vitro, one may infer that the effect on the renin system is indirect rather than directly mediated at the level of renal juxtaglomerular cells.
 ...
PMID:T-type and L-type calcium channel blockers exert opposite effects on renin secretion and renin gene expression in conscious rats. 964 84

This study aimed to assess the relevance of specific potassium channels, such as inwardly or outwardly rectifying and calcium-regulated potassium channels, to the control of renin secretion. For this purpose we examined the effects of the K+ channel blockers 4-aminopyridine (1 mmol/l), barium (100 micromol/l), tetraethylammonium (2 mmol/l) and apamin (200 nmol/l) on basal renin secretion, on renin secretion stimulated by isoproterenol (10 nmol/l) and on the inhibition of renin secretion by angiotensin II (100-300 pmol/l) in the isolated rat kidney perfused at constant pressure. Whilst all four K+ channel blockers increased renal vascular resistance, only 4-aminopyridine and barium attenuated isoproterenol-stimulated renin secretion in an additive fashion and augmented the inhibitory effect of angiotensin II. These effects of K+ channel blockers were not changed by the L-type calcium channel blocker amlodipine (5 pmol/l), indicating that their effects on renin secretion are not due to voltage-operated calcium influx. Our data, moreover, suggest that potassium efflux from renal juxtaglomerular cells is not important for the inhibitory action of angiotensin II on renin secretion. As a consequence it appears that the membrane potential of renal juxtaglomerular cells per se is relevant to renin secretion such that membrane depolarization inhibits the exocytosis of renin whilst hyperpolarization favors renin secretion. By their activity, potassium channels can contribute to membrane hyperpolarization and thus facilitate renin secretion.
 ...
PMID:Role of potassium channels in the control of renin secretion from isolated perfused rat kidneys. 1104 55

The renin-angiotensin system plays an important role in the development of diabetic nephropathy. However, the mechanism of ANG II receptor regulation in the renal proximal tubule in the diabetic condition has not been elucidated. Thus we investigated the signal pathways involved in high-glucose-induced downregulation of ANG II binding in primary cultured renal proximal tubule cells. Twenty-five millimolar glucose, but not mannitol and L-glucose, induced downregulation of the AT(1) receptor (AT(1)R) because of a significant decline in maximal binding with no significant change in the affinity constant. Twenty-five millimolar glucose also decreased AT(1)R mRNA and protein levels. The 25 mM glucose-induced increase in the formation of lipid peroxides was prevented by antioxidants, protein kinase C (PKC) inhibitors, or L-type calcium channel blockers. These agents also blocked 25 mM glucose-induced downregulation of (125)I-ANG II binding. In addition, 25 mM glucose increased transforming growth factor (TGF)-beta1 secretion, and anti-TGF-beta antibody significantly blocked 25 mM glucose-induced downregulation of (125)I-ANG II binding. Furthermore, the 25 mM glucose-induced increase in TGF-beta1 secretion was inhibited by PKC inhibitors, L-type calcium channel blockers, or antioxidants. In conclusion, high glucose may induce downregulation of (125)I-ANG II binding via a PKC-oxidative stress-TGF-beta signal cascade in primary cultured rabbit renal proximal tubule cells.
 ...
PMID:The mechanism of angiotensin II binding downregulation by high glucose in primary renal proximal tubule cells. 1178 36

Acute hypoxia induces a decrease in plasma renin activity (PRA), mediated, e.g., by an increase in adenosine concentration, calcium channel activity, or inhibition of ATP-sensitive potassium channels. The decrease in PRA results in a decrease in angiotensin II (AngII) and plasma aldosterone concentration (PAC). This study investigates whether these hypoxia-induced mechanisms can be inhibited by the L-type voltage-dependent calcium channel antagonist nifedipine. Eight conscious, chronically tracheotomized dogs received a low sodium diet (0.5 mmol Na x kg body wt(-1) x day(-1)). The dogs were studied twice in randomized order, either with nifedipine infusion (1.5 microg x kg body wt(-1) x min(-1), Nifedipine) or without (Control). The dogs were breathing spontaneously: first hour, normoxia [inspiratory oxygen fraction (FiO2)=0.21]; second and third hour hypoxia (FiO2=0.1). In Controls, PRA (6.8+/-0.8 vs. 3.0+/-0.5 ngAngI x ml(-1) x min(-1)), AngII (13.3+/-1.9 vs. 7.3+/-1.9 pg/ml), and PAC (316+/-50 vs. 69+/-12 pg/ml) decreased during hypoxia (P<0.05). In Nifedipine experiments, PRA (6.5+/-0.9 vs. 10.5+/-2.4 ngAngI x ml(-1) x min(-1)) and AngII (14+/-1.1 vs. 18+/-3.9 pg/ml) increased during hypoxia, whereas the decrease in PAC (292+/-81 vs. 153+/-41 pg/ml) was blunted (P<0.05). These results foster the idea that the hypoxia-induced decrease in PRA involves L-type calcium channel activity.
 ...
PMID:Nifedipine inhibits the hypoxia-induced decrease in plasma renin activity in conscious dogs. 1283 17

Hypertensive patients characteristically exhibit left ventricular (LV) hypertrophy and diastolic dysfunction. The effects of antihypertensive agents on LV hypertrophy and diastolic dysfunction do not always correlate with the degree of blood pressure reduction, but their effects on the sympathetic nervous system and renin-angiotensin system (RA system) are thought to be important. We investigated the effects of amlodipine and cilnidipine, N- and L-type calcium channel antagonists that suppress both blood pressure elevation and sympathetic activities, on LV hypertrophy and diastolic function. Patients with essential hypertension were randomly assigned to receive either amlodipine, cilnidipine or nifedipine CR (which does not block N-type calcium channels) for 6 months. The LV mass index was determined using M-mode echocardiography. The E/A ratio, i.e., the ratio of maximum amplitude between the early diastolic wave (E wave) and the atrial systolic wave (A wave) in the LV inflow pattern, and the deceleration time for the E wave were determined using pulse Doppler echocardiography. Systolic and diastolic blood pressures significantly decreased from the baseline values in all three groups, with no significant differences among the groups. The LV mass index had significantly decreased when it was evaluated 3 months after the initiation of treatment in the cilnidipine group and when it was evaluated 6 months after the initiation of treatment in the amlodipine group; only a slight decrease was observed in the nifedipine CR group. A significant decrease in the deceleration time and a significant increase in the E/A ratio were observed after 3 months of treatment in the cilnidipine and amlodipine groups but not in the nifedipine CR group. Thus, the effects of long-acting calcium channel antagonists on hypertensive LV hypertrophy and LV diastolic function varied from one antagonist to the other. Left ventricular hypertrophy and diastolic function improved in the cilnidipine and amlodipine groups, but not in the nifedipine CR group. These results indicate that the suppression of sympathetic nerve activity by the blockade of N-type calcium channels contributes to the improvement of LV hypertrophy and diastolic function.
 ...
PMID:Effects of calcium channel antagonists on left ventricular hypertrophy and diastolic function in patients with essential hypertension. 1464 10

The sympathetic nerve activity plays an important role on the renal function through the vasoactive system and the renin-angiotensin system. Although interest in the renal protective effects of anti-sympathetic agents has been increased, there are not enough data to clarify this efficiency. Therefore, we investigated the effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injury in Dahl salt-sensitive (Dahl S) rats. Male Dahl S rats (6 weeks of age) were fed a high salt (4% NaCl) diet. They were divided into groups with similar blood pressure at 12 weeks of age and they received vehicle (n=7) or cilnidipine (30 mg/kg/d as food admix, n=9) for 8 weeks. Cilnidipine treatment suppressed the increase in systolic blood pressure. Although urinary protein excretion was not influenced, cilnidipine inhibited the increase in blood urea nitrogen and decrease in creatinine clearance. Histological investigation revealed that progression of glomerular sclerosis was inhibited in cilnidipine treatment group. Of notes, cilnidipine reduced plasma norepinephrine level and plasma rennin activity compared with vehicle-treated Dahl S rats. These data indicated that cilnidipine has suppressive effects against progressive renal injury in Dahl S rats. This effect is not only explained by the L-type calcium channel blocking action that lowered blood pressure, but also partially explained by the N-type calcium channel blocking action that lead to suppression of the sympathetic nerve activity and renin-angiotensin system.
 ...
PMID:Effects of L/N-type calcium channel antagonist, cilnidipine on progressive renal injuries in Dahl salt-sensitive rats. 1665 22

Effects of a new lipophilic L-type calcium channel blocker, azelnidipine, on the expression of molecular components of the renin-angiotensin-aldosterone system (RAAS) were assessed. Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of diabetes with hypertension, and their lean littermates, Long-Evans Tokushima Otsuka (LETO) rats, were treated with azelnidipine for 2 weeks. The renal cortical mineralocorticoid receptor mRNA in OLETF was higher than in LETO, but was suppressed (P<0.05) by azelnidipine. Renal cortical angiotensin-converting enzyme mRNA of OLETF was lower than that of LETO rats, and it was further suppressed by azelnidipine (P<0.05). Azelnidipine can down-regulate the gene expression of molecular components of RAAS.
 ...
PMID:Azelnidipine down-regulates renal angiotensin-converting enzyme and mineralocorticoid receptor mRNA in diabetic hypertensive rats. 1703 Oct 66

During a couple of decades, a number of antihypertensive drugs have been developed, and the choice of hypertension treatment has been expanded. Among antihypertensive drugs, calcium channel blockers, which inhibit L-type voltage-gated calcium channels, are potent vasodilators, and have been used as a first- or second-line drug. Dihydropyridine-class calcium channel blockers are categorized into three generations according to the length of activity, and long-acting calcium channel blockers cause less activation of sympathetic nervous system, and are reported to offer beneficial action compared with short-action agents. Furthermore, novel types of calcium channel blockers have been developed that possess the blocking action on other calcium channel subtypes (T- and N-type), and exert agent-specific action apart from their class effects, such as the effects on heart rate and renin/aldosterone release. These additional benefits conferred by T/N-type calcium channel blockade are anticipated to provide organ protective actions in the treatment of hypertension, in addition to the blood pressure-lowering effect of L-type calcium channel blockade. In conclusion, novel calcium channel blockers with sustained activity and T/N-type calcium channel blocking action could provide more beneficial effects than classical blockers, and may expand the clinical utility of these agents.
 ...
PMID:New Generation Calcium Channel Blockers in Hypertensive Treatment. 1982 1


1 2 Next >>