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)

Adding converting-enzyme inhibitors to the salt depleted state is marked by a reduction in blood pressure despite compensatory increases in heart rate and plasma norepinephrine. This study investigated whether this increase in sympathetic function is also accompanied by an increase in beta-adrenergic receptor function. Ten subjects were studied following two separate five day hospitalizations on 10 mEq sodium diets while receiving either placebo or captopril. During low sodium with captopril, blood pressure and angiotensin II decreased, while heart rate, renin, norepinephrine and isoproterenol-stimulated cyclic AMP accumulation in lymphocytes increased. The results indicate that enhanced beta-adrenergic receptor function does accompany sympathetic activation during sodium restriction and converting enzyme inhibition and further support studies showing that the renin-angiotensin system plays the dominant role in blood pressure regulation in the sodium depleted state.
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PMID:Beta-adrenergic receptor sensitivity during sodium restriction and converting enzyme inhibition. 216 1

Prostacyclin (PGI2) is known to cause vasorelaxation and inhibit platelet aggregation by receptor-mediated mechanisms. While cyclic (c)AMP is known to act as a second messenger for platelet aggregation, vasorelaxation by hyperpolarization has been described only recently and may provide an explanation, in addition to stimulation of cAMP, for the PGI2 mechanism of action on blood vessels. When PGI2 is infused into healthy volunteers it reduces blood pressure only at infusion rates that also cause significant side effects, primarily nausea, emesis, flushing, diphoresis and restlessness. In hypertensive patients blood pressure responses are complex and are influenced to some extent by secretion. PGI2 stimulates renin secretion by a direct effect on the juxtaglomerular apparatus, and also has an indirect effect by activating the sympathetic nervous system. Thus it is useless as an antihypertensive agent even apart from its debilitating side effects. Vascular PGI2 is synthesized endogenously by both the endothelial cells and the muscularis of arteries. While the endothelial cells undoubtedly synthesize larger amounts of PGI2, the muscularis comprises a much larger tissue mass so that the overall synthesis is about equally distributed between the endothelial and muscle cells. In patients with pregnancy-induced hypertension and some patients with essential hypertension, endogenous synthesis of PGI2 has been evaluated by measuring 2,3-dinor-6-keto-PGF1 alpha and has proved to be defective. Some drugs (cicletanine, thiazides, propranolol) have been shown to stimulate PGI2 synthesis, and inhibition of cyclooxygenase has been shown to abolish their antihypertensive effects. Whether stimulation of PGI2 synthesis affects the antihypertensive efficacy of these drugs is not yet known.
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PMID:Prostacyclin in hypertension. 225 88

In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg body wt) 27 mmol/day Pi and 52 mEq/day K+, we increased diet K+ to 156 mmol/day with supplements first of potassium bicarbonate (KHCO3) alone and then of potassium chloride (KCL) alone, each for eight days interrupted by an eight-day recovery period of no K+ supplement. Urine Pi decreased promptly with either K(+)-salt, each inducing a persisting retention of 7 to 10 mmoles Pi, which was dumped during recovery. Fasting serum [Pi] increased with either K+ supplement (P = 0.022, repeated measures analysis of variance); the composite mean serum [Pi] for the two K(+)-supplement periods exceeded that for the two periods without supplements (P less than 0.01, paired t-test). Conversely, the concentrations of serum calcitriol decreased with either K+ supplement (P = 0.020). Among subjects, the diet K(+)-induced increases in serum [Pi] correlated with those in plasma [K+] (r = 0.64, P = 0.027); the decreases in serum calcitriol concentration correlated with the increases in serum [Pi] (r = -0.69, P = 0.014). There were no significant differences among periods in serum parathyroid hormone, ionized calcium, urine cyclic AMP excretion, plasma renin activity, body weight, serum albumin, or creatinine clearance; plasma volume decreased slightly during KCL but not during KHCO3 periods.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dietary potassium influences kidney maintenance of serum phosphorus concentration. 234 30

Various studies have shown that a high protein (HP) diet, compared to a low protein (LP) diet, leads to hypercalciuria and alterations in renal and systemic hemodynamics. The authors compared the effects of HP diet to those of normal protein diet (NP) to determine the possible mechanisms by which changes in systemic hemodynamics and hypercalciuria occurred. The studies were conducted in awake rats; the effects of dietary sodium content on the changes induced by HP also were evaluated. The relationship of prostaglandins (PG), renin (PRA), and aldosterone (PA) to changes in blood pressure (BP) was assessed. Two weeks after HP and normal sodium feeding (40%), glomerular filtration rate (GFR) and urine flow (V) were not different from the same values in a group on an NP diet (23%). When HP was fed with low sodium, there was a rise in V as a consequence of greater fluid intake. Although plasma calcium remained constant, the hypercalciuria correlated with high protein and sodium content. Alterations in 1,25(OH)2 vitamin D3 or PTH (cyclic AMP excretion) function did not explain the hypercalciuria induced by HP. This suggests that HP leads to inhibition of tubular calcium reabsorption by mechanism(s) yet to be elucidated. Although HP did not alter GFR, it led to an increase in BP, a fall in renal vascular resistance, and an increase in RPF, regardless of sodium intake. PRA and urine PGE2 excretion were significantly higher in the rats on HP diet, whereas PA remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal and systemic effects of short-term high protein feeding in normal rats. 254 89

Modulation of renin synthesis by lipoxygenase products has been studied in cultured human mesangial cells under basal conditions and in the presence of prostaglandin (PG) E2. Total renin and cyclic AMP productions were stimulated in a dose-dependent manner (0.1-10 microM) by PGE2. The stimulatory effect of PGE2 on renin production was inhibited by 12-hydroxyeicosatetraenoic acid (12-HETE) between 0.1 and 100 nM. Extracellular and intracellular renin were affected similarly. Neither basal and PGE2-dependent cyclic AMP nor basal cyclic GMP productions were modified. 15-Hydroxyeicosatetraenoic acid (15-HPETE), 12-hydroperoxyeicosatetraenoic acid (12-HPETE) and 15-hydroperoxyeicosatetraenoic acid (15-HPETE) had the same effects as 12-HETE. Intracellular calcium concentration was not modified in the presence of 12-HETE. Since oleyl-2-acetylglycerol (OAG), an analog of diacylglycerol, also inhibited PGE2-stimulated renin production, it is hypothesized that the effect of the lipoxygenase products is mediated via protein kinase C stimulation.
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PMID:Modulation of renin synthesis by lipoxygenase products in cultured human mesangial cells. 254 91

Renal arterial infusion of acetylcholine (ACh) in the dog normally produces a sustained rise in sodium excretion (UNaV) and in renal plasma flow (RPF). When prostaglandin (PG) synthesis is inhibited, ACh induces only a transient increase in UNaV and RPF followed by a progressive decline in UNaV and RPF, and a rise in renin secretory rate (RSR). Renal arterial infusion of PGE2 but not a vasodilator such as bradykinin restored the response to ACh to normal in indomethacin (Indo)-treated dogs. During renal arterial infusion of dibutyryl cyclic AMP (6 mg/min), ACh also produced a sustained increase in UNaV and RPF despite an inhibition of PG synthesis by Indo. Renal arterial infusion of verapamil (60 micrograms/min) or diltiazem (60 micrograms/min) also prevented the subsequent fall in RPF when ACh was infused; RSR, however, did not show a rise. The results suggest that synthesis of PGE2 with stimulation of cAMP is required for sustained ACh action. When PGE synthesis is inhibited, ACh may produce renal vasoconstriction by increasing intracellular Ca2+ concentration. The partial effect of calcium channel blockers suggests that release of calcium from intracellular stores as well as calcium entry may mediate the response.
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PMID:Ca2+ antagonists and db-cAMP sustain a rise in renal blood flow induced by acetylcholine in indomethacin-treated dogs. 254 65

We recently showed that the administration of the antidiuretic V2 specific agonist, 1-desamino[8-D-arginine]vasopressin (dDAVP), to seven male patients with congenital nephrogenic diabetes insipidus (CNDI) did not cause a decrease in blood pressure nor an increase in plasma renin activity or factor VIIIc or von Willebrand factor release. In normal subjects, plasma renin activity, coagulation factors and plasma cyclic AMP are stimulated not only by dDAVP but also by the administration of epinephrine. In the present study, we measured tissue plasminogen activator (activity and antigenicity), von Willebrand factor multimers, plasma and urinary cyclic AMP concentrations following dDAVP or epinephrine administration. We infused epinephrine into three male patients with CNDI. Factor VIIIc and tissue plasminogen activator augmented by 75 to 100% and von Willebrand Factor multimers were increased; plasma renin activity and plasma cyclic AMP concentration increased by 200%. None of these values changed when the same subjects as well as eleven other male patients with CNDI received dDAVP. Furthermore, dDAVP administration increased plasma cyclic AMP concentrations in normal subjects, but not in 14 male patients with CNDI. These results demonstrate the specificity of the extrarenal V2 receptor defect expressed in our patients. The lack of a plasma cyclic AMP response to the administration of dDAVP would suggest an altered pre-cyclic AMP stimulation mechanism.
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PMID:Epinephrine and dDAVP administration in patients with congenital nephrogenic diabetes insipidus. Evidence for a pre-cyclic AMP V2 receptor defective mechanism. 255 38

1. Using a renal cortical slice preparation from the summer-active ground squirrel, Spermophilus lateralis, resting renin release (RR) and tissue cyclic AMP content (TcAMPC) levels were found to be significantly higher and lower, respectively, than those previously reported for its hibernating counterpart. 2. At a 10(-5) M dose, PGE2 but not PGE1, PGF2-alpha or PGA1, significantly stimulated RR in the summer-active ground squirrel (SAGS). 3. Addition of agents which normally increase TcAMPC significantly potentiated the effect of PGE1, while preventing that of PGE2, on RR and TcAMPC. 4. Opposite TcAMPC changes may mediate the in vitro RR responses to PGE1 and PGE2 administration in the SAGS.
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PMID:Renin release responses to in vitro prostaglandin challenge in the summer-active ground squirrel, Spermophilus lateralis. 257 41

We have previously reported that the strong diuresis, natriuresis and urinary cyclic GMP excretion after acute volume loading in rats are caused by ANP and can be blocked by additionally given monoclonal antibodies directed against ANP. The present report describes that in contrast to the changes in ANP and cyclic GMP, the plasma renin activity and aldosterone concentration are decreased after volume loading. This decrease is completely blocked by simultaneous administration of the monoclonal antibodies. Plasma cyclic AMP levels are not affected. From this study it seems to be clear that the inhibition of the renin-aldosterone system is not a direct effect of volume expansion but is specially mediated by the released ANP.
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PMID:The reduction of renin and aldosterone as a response to acute hypervolemia is blocked by a monoclonal antibody directed against atrial natriuretic peptides. 282 95

1. The hypokalaemia-inducing effects of two widely used inhaled antiasthmatic beta 2-adrenoceptor agonists, fenoterol and salbutamol, were compared in six healthy male volunteers. 2. Each drug was administered in three different doses, 400, 600 and 800 micrograms, which were repeated three times with 30 min intervals (total doses 1200, 1800 and 2400 micrograms in 1 h). The treatments were given at 1 week intervals in random order in a single-blind fashion. 3. The concentration of potassium in plasma was dose-dependently reduced by both drugs with peak effects 75-90 min after the first inhalations. The hypokalaemic effect of fenoterol was significantly greater than that of equal doses of salbutamol (average +/- s.d. reductions of 1.13 +/- 0.32 and 0.67 +/- 0.25 mEq l-1, respectively, after the highest doses, P less than 0.05). Concomitantly, decreases were noted in the amplitude of the T-wave on the ECG. 4. The concentration of cyclic AMP in plasma was measured and used as an indicator of systemic beta 2-adrenoceptor agonistic effects of the drugs. Increases in cAMP were a close mirror image of the drugs' effects on potassium in plasma. 5. Plasma renin activity, noradrenaline in plasma and heart rate were also dose-dependently increased by the treatments, whereas blood pressure remained unaltered. 6. While the clinical significance of hypokalaemia induced by inhaled beta 2-adrenoceptor sympathomimetics still is a matter of debate, our results point to possible differences between therapeutically equipotent doses of fenoterol and salbutamol in their propensity to cause hypokalaemia and other acute non-bronchial effects.
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PMID:Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers. 282 53


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