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)

Prazosin is a post synaptic alpha adrenergic blocker effective in hypertension, whose hypotensive effect is unaccompanied by reflex tachycardia or hyperreninemia, nor by other evidence of increased sympathetic activity. We studied the baroreceptor reflex arc as a potential mediator of these effects. Twenty-two essential hypertensive men were treated with prazosin alone versus placebo, and experienced a blood pressure fall (from 114.8 +/- 3.6 down to 101.1 +/- 2.5 mmHg, p less than 0.005) unaccompanied by any change in heart rate, plasma renin activity, or several other indices of sympathetic nervous system activity (plasma dopamine-beta-hydroxylase activity; urinary excretion of free catecholamines and vanillyl mandelic acid; all p less than 0.1). Concomitant with the blood pressure fall, there was a significant depression of baroreflex arc sensitivity, from 11.4 +/- 2.0 ms/mmHg down to 6.6 +/- 1.9 ms/mmHg (p less than 0.05), without an associated change in cardiac vagal inhibition (291.2 +/- 46.2 versus 300.3 +/- 19.2 ms, p greater than 0.1). Baroreflex arc sensitivity depression may in part explain the lack of reflex sympathetic outflow noted during prazosin treatment of hypertension.
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PMID:Prazosin depression of baroreflex function in hypertensive man. 704 70

Prazosin improves hemodynamics promptly in patients with congestive heart failure (CHF), but tolerance to repeated doses may develop rapidly. To determine if the kidneys play a role in this attenuation of effect, we studied renal responses in nine CHF patients treated with prazosin (5 mg three times a day for 3 days) preceded and followed by 3 days of placebo. Prazosin decreased mean arterial blood pressure from 87.0 +/- 2.2 (mean +/- SEM) to 84.0 +/- 2.0 mm Hg (p < 0.05) with no change in heart rate (73.1 +/- 3.3 bpm on placebo and 73.6 +/- 3.5 bpm on prazosin). The change in creatinine clearance from 81.6 +/- 8.7 to 96.3 +/- 10.4 ml/min with prazosin was not statistically significant, but the slight increase in urine volume from 2.33 +/- 0.22 to 2.51 +/- 0.23 1/24 hr was (p < 0.01). There were no significant changes in serum sodium, potassium, chloride, CO2, blood urea nitrogen, osmolality or glucose, urinary excretion of sodium or potassium, or sodium balance. The data were analyzed for changes within each period but there were no significant changes from day to day. Plasma renin activity rose from 3.93 +/- 0.69 to 4.96 +/- 0.84 ng/ml/hr during prazosin (p < 0.02). Significant alterations in renal function are not likely when patients with CHF are treated with prazosin, and any attenuation of effect of prazosin after repeated doses is not likely due to mechanisms involving alterations in renal function.
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PMID:Effect of prazosin on renal function in congestive heart failure. 740 92

Prazosin was give for 10 to 14 days to eight hypertensive patients on a fixed intake of dietary salt. Except as limited by side effects, the dose was increased from 2 mg/day to a maximum dose of 24 mg/day. During treatment, when subjects were studied in supine and upright positions, mean arterial pressure (MAP) fell 6% and 12% (p less than 0.025 and p less than 0.005), heart rate rose 3% and 9% (p less than 0.05 and p less than 0.005), and plasma norepinephrine increased 95% and 107% (p less than 0.01 and p less than 0.001) over control. Daily excretion of the norepinephrine metabolites methoxyhydroxyphenyl glycol (MHPG) and vanillylmandelic acid (VMA) increased 42% and 17% (p less than 0.05 for each) during treatment. There were no changes in average body weight or plasma renin for the group, but patients whose body weight increased tended to show less reduction in blood pressure (correlation coefficient, r = 0.72, p less than 0.05) and smaller increases in heart rate (r = -.073, p less than 0.05) during treatment with prazosin. These data suggest that expansion of extracellular fluid and activation of the sympathetic nervous system oppose the hemodynamic effects of prazosin.
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PMID:Physiologic mechanisms opposing the hemodynamic effects of prazosin. 746 Apr 77

While the interactions between angiotensin II (Ang II) and norepinephrine (NE) on cardiovascular responses are well known, their effects on renin responses are not. We determined the renin secretion rate (RSR) and intracellular calcium level in juxtaglomerular cells harvested from Sprague-Dawley rats using a radioimmunoassay and a two-dimensional calcium analyzer. The effect of Ang II and NE was inhibitory on RSR and stimulatory on intracellular calcium. The NE-induced RSR response was amplified in the presence of Ang II (20 nmol/l). The NE-induced intracellular calcium response was also potentiated by the Ang II. There was a significant correlation (r = 0.994, p < 0.0001) between the changes in the RSR and those in intracellular calcium levels. Losartan (0.1 mumol/l). an Ang II type 1 receptor antagonist, blocked the Ang II threshold RSR responses and completely abolished the Ang II-related enhancements. The exclusion of calcium from the buffer reduced the maximal RSR response to NE but did not prevent the enhancement, suggesting the importance of the mobilization of intracellular calcium in the mechanism. The Ang II-induced RSR was amplified in the presence of NE (0.2 mumol/l). The Ang II-induced intracellular calcium response was also potentiated by the NE. A significant correlation (r = 0.996, p < 0.0001) between the changes in the RSR and the changes in intracellular calcium levels was also noted. Prazosin (1 mumol/l), an alpha 1-adrenoceptor antagonist, blocked the NE threshold RSR responses and abolished the agonist-related enhancements. The calcium-free buffer diminished this amplication with a slight decrease in the maximum RSR response to Ang II.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Interactions between angiotensin II and norepinephrine on renin release by juxtaglomerular cells. 758 79

The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) and heart rate (HR) variability responses to air-jet stress was assessed in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. Activity of the encogenous RAS was suppressed by chronic treatment by a nonpeptide angiotensin II receptor antagonist (Iosartan). The role of alpha 1-adrenoceptor activity was evaluated in rats by acute administration of prazosin. In untreated animals, an air jet induced an increase in systolic BP (SBP; 9 +/- 2 mmHg for WKY and 8 +/- 2 mmHg for SHR) and in HR (56 +/- 19 beats/min for WKY and 76 +/- 8 beats/min for SHR), followed by an increase of the midfrequency (MF; 0.2-0.6 Hz) component of HR in WKY (183%) and by an increase of the MF component of SBP and diastolic BP in SHR (65%). Prazosin prevented BP rises as well as the MF component of BP and HR increases associated with air-jet stress. Chronic suppression of the RAS by losartan did not alter the BP response to the air jet in WKY and slightly reduced it in SHR but abolished all the BP and HR variability changes in both strains. These results indicate that the SNS but not RAS is essential for the BP rise induced by stress and demonstrate that RAS in conjunction with SNS is involved in BP and HR variability changes associated with stress.
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PMID:Role of angiotensin II and catecholamines in blood pressure variability responses to stress in SHR. 876 93

The antihypertensive effects of an angiotensin II antagonist, candesartan cilexetil (TCV-116), and other classes of antihypertensive drugs (including a calcium antagonist, manidipine; a diuretic, hydrochlorothiazide (HCTZ); an alpha-blocker, prazosin; and a beta-blocker, atenolol) administered in combination were examined in spontaneously hypertensive rats by oral administration daily for 2 wk. TCV-116 at 1 mg/kg lowered the blood pressure by about 50 and 30 mmHg, 5 and 24 h after dosing, respectively. The blood pressure was slightly lowered by HCTZ at 10 mg/kg, but it was synergistically reduced when HCTZ was given in combination with TCV-116. Manidipine at 3 mg/kg lowered the blood pressure by about 50 mmHg 1 h after administration. When manidipine was given in combination with TCV-116, blood pressure was reduced additively. Prazosin at 1 mg/kg lowered the blood pressure by 40 to 50 mmHg 1 h after dosing. When prazosin was given in combination with TCV-116, the reduction was intensified more than additively, to about 100 mmHg. Atenolol at 50 mg/kg lowered the blood pressure by 10 to 20 mmHg 5 h after dosing. Even when atenolol was administered in combination with TCV-116, the reduction in blood pressure was virtually the same as that observed when TCV-116 was given alone. TCV-116 and HCTZ had no effect on the pulse rate, whereas manidipine and prazosin both increased it, owing to reflex tachycardia, and atenolol decreased it. TCV-116 had no effect on the change in the pulse rate induced by these antihypertensive drugs and no effect on HCTZ-induced diuresis. TCV-116 and HCTZ each caused a significant increase in plasma renin concentration (PRC), and prazosin caused a slight elevation. Manidipine had no effect on the PRC, whereas atenolol reduced it. Given in combination with TCV-116, these antihypertensive drugs had the same effect on the elevated PRC induced by TCV-116 as they did on the basal PRC when administered alone. These results suggest that antihypertensive drugs that cause compensatory activation of the renin-angiotensin system have more marked antihypertensive activity when given in combination with TCV-116, but that there will is no combined effect on the pulse rate.
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PMID:Combined effects of the angiotensin II antagonist candesartan cilexetil (TCV-116) and other classes of antihypertensive drugs in spontaneously hypertensive rats. 898 55

1. A hormonal-sympathetic reflex model for long-term control of arterial pressure is presented. It is hypothesized that the hormonal-sympathetic reflex regulates arterial pressure during chronic dietary salt loading by decreasing sympathetic tone. This sympathetic response is mediated by an increase in plasma vasopressin (AVP) and a decrease in plasma angiotensin (AngII). 2. Three new models of neurogenic salt-dependent hypertension are presented. All models are theoretically based on an impaired hormonal-sympathetic reflex. 3. In the first model, sympathetic responsiveness is 'clamped' by long-term alpha-adrenergic blockade with prazosin. Prazosin treated rats exhibit marked salt-dependent hypertension despite normal suppression of the renin-angiotensin system. 4. In the second model, the ability of the central nervous system to respond to salt-induced changes in AVP and AngII concentrations was prevented by long-term administration of antagonists selective for the AVP-V1 and AT1. This 'clamp' of the afferent hormonal signal resulted in salt-dependent hypertension identical in magnitude to that observed in prazosin treated rats. 5. In the third model, the long-term arterial pressure responses to increasing dietary salt were examined in sino-aortic denervated (SAD) rats. SAD rats exhibited salt-dependent hypertension, of lesser magnitude than that observed with 'clamped' afferent and efferent pathways of the hormonal-sympathetic reflex. 6. A primary role for hormonal 'error signals' is presented and the impact this perspective has on past and future investigations of central mechanisms of long-term arterial pressure regulation is discussed.
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PMID:Hormones as long-term error signals for the sympathetic nervous system: importance of a new perspective. 904 15

We have previously shown that sodium restriction upregulates the genes encoding angiotensin II receptor (AT1) subtypes, AT1A and AT1B, in the adrenal gland and that this upregulation is mediated by activation of the AT1 receptor. There are multiple interactions between the renin-angiotensin and the adrenergic nervous systems; thus, we conducted the present experiment to investigate whether low sodium-induced upregulation of adrenal AT1A and AT1B is modulated by the alpha1-adrenoreceptor. Seven-week-old male Wistar rats were divided into four groups and given normal sodium diet (0.5%, NS), NS+prazosin (3.5 microg x kg(-1) x min(-1) by osmotic pump), low sodium diet (0.07%, LS), or LS+prazosin. Body weight and mean arterial pressure were not modified over the 2 weeks of treatment (P>.05). Pressor responses to bolus injection of the alpha1-agonist phenylephrine were inhibited in both prazosin groups, compared with NS and LS rats (P<.05). Adrenal AT1A mRNA, determined by Northern blot analysis, was increased in LS (P<.05) but not in NS+prazosin (P>.05), compared with NS. Prazosin enhanced the LS-induced increase of AT1A mRNA (P<.05). Adrenal AT1B mRNA was increased in both LS and NS+prasozin rats, compared with NS rats (P<.05). Prazosin also enhanced the LS-induced increase in AT1B mRNA (P<.05). Therefore, blockade of alpha1-adrenoreceptor results in an enhancement of LS-induced upregulation of adrenal mRNA for AT1A and AT1B. These data suggest that the sympathetic nervous system exerts an inhibitory action, via activation of the alpha1-adrenoreceptor, on AT1A and AT1B gene expression in the adrenal gland during sodium depletion.
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PMID:Regulation of type 1 angiotensin II receptor in adrenal gland: role of alpha1-adrenoreceptor. 931 15

Transgenic TGR(mREN2)27 rats (TGR), carrying an additional mouse renin gene, are characterized by severe hypertension, an inverse circadian blood pressure profile, a blunted response to photic entrainment signals, and an increased nocturnal production of the pineal hormone melatonin. In order to evaluate the contribution of the over-expressed renin-angiotensin system to the function of the pineal gland in TGR, we studied the adrenergic and angiotensin II (Ang II)-mediated regulation of melatonin synthesis using dispersed pinealocytes from TGR and from Sprague-Dawley control rats (SDR). Isoproterenol was more effective in stimulating melatonin release in pinealocytes from TGR than from SDR, whereas the maximum effect of norepinephrine (NE) stimulation did not differ between the strains. Prazosin reduced the NE-mediated melatonin release only in SDR but not in TGR pinealocytes. Competition experiments with (+/-)-, (+)-, (-)-propranolol and (+/-)-atenolol revealed one homogeneous population of beta1-adrenoceptors. Ang II had no significant effect on basal or isoproterenol-induced melatonin release in either strain. In conclusion, TGR pinealocytes were more sensitive to beta-adrenergic stimulation than SDR pinealocytes, but lacked the alpha1-adrenergic potentiation of beta-adrenergic induced melatonin release. The renin-angiotensin system was not directly involved in the regulation of melatonin synthesis by rat pinealocytes in vitro.
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PMID:Altered melatonin production in TGR(mREN2)27 rats: on the regulation by adrenergic agonists, antagonists and angiotensin II in cultured pinealocytes. 1158 61

The renin-angiotensin (RAS) and the alpha1 sympathetic nervous system (SNS) interact at different levels in cardiovascular regulation. Concurrent use of angiotensin-converting enzyme (ACE) inhibitors and alpha1 receptor antagonists result in a synergistic antihypertensive action and is of wide utility in cardiovascular therapy. We examined the impact of concurrent inhibition of RAS (captopril or losartan) and the SNS (prazosin) before and after acute nitric oxide (NO) synthase inhibition with L-nitro-L-arginine methyl ester (L-NAME) on renal cortical perfusion (RCF) and blood pressure (MAP) in healthy and acute ischemic renal failure (ARF) rats (n = 6). Captopril or losartan reduced MAP and increased RCF more in healthy (p < 0.001) and ARF rats (p < 0.02). Prazosin alone reduced both MAP and RCF (p < 0.001). The combination of prazosin with captopril or losartan caused an additive fall in MAP, and mitigated the fall in RCF. Captopril + prazosin caused a profound fall in RCF following L-NAME, in healthy but not ARF rats (p < 0.001). Acetylcholine (Ach), a vasodilator which stimulates endogenous NO production caused a profound paradoxical fall in RCF in ARF, but not in healthy rats (p < 0.001 ANOVA). These results indicate a significant interaction between angiotensin II and phenylephrine in renal vasomotion. It establishes that endogenous NO homeostatically opposes angiotensin II-alpha1-mediated renal vasoconstriction, and that the vasodilator role of NO is diminished in ARF. The paradoxical fall in RCF induced by Ach in ARF is speculated to result, at least in part, from the formation of peroxynitrite (ONOO-), which acts as a renal vasoconstrictor, following the combination of ischemia-generated super oxide anion (O-2), with endothelial NO released by Ach.
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PMID:Interactions of the renin-angiotensin system and alpha-1 adrenoceptors on renal hemodynamics in healthy and acute renal failure rats: the role of nitric oxide. 1180 63


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