Prazosin: Preliminary Clinical and Pharmacological Observations

1974 ◽  
Vol 48 (s2) ◽  
pp. 177s-179s ◽  
Author(s):  
P. Bolli ◽  
A. J. Wood ◽  
E. L. Phelan ◽  
D. R. Lee ◽  
F. O. Simpson
Keyword(s):  
Blood Pressure ◽  
Nervous Activity ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Exchangeable Sodium ◽  
Standing Posture ◽  
Molar Basis ◽  
Genetically Hypertensive Rats ◽  
Volume Tolerance

1. Prazosin had a considerable anti-hypertensive effect in both lying and standing posture in a mixed group of twenty-four patients in an open clinical trial. The drug was well tolerated and side-effects were few. 2. Tested on rat blood vessels, prazosin was ten times more potent on a molar basis than phentolamine in blocking the vasoconstrictor effects of noradrenaline. In the absence of vasoconstrictor nervous activity, no vasodilatation was observed. 3. In genetically hypertensive rats, prazosin in large doses caused a substantial fall in blood pressure, total exchangeable sodium and extracellular fluid volume. Tolerance to these effects started to develop within 20 days. In normotensive rats, blood pressure was lowered but total exchangeable sodium and extracellular fluid volume were not affected.

Relation of saluretic and hypotensive effects of hydrochlorothiazide in the rat

1960 ◽  
Vol 198 (1) ◽  
pp. 148-152 ◽  
Author(s):  
Sydney M. Friedman ◽  
Miyoshi Nakashima ◽  
Constance L. Friedman
Keyword(s):  
Blood Pressure ◽  
Plasma Volume ◽  
Extracellular Space ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Urinary Volume ◽  
Hypertensive Rats ◽  
Inulin Space

Hydrochlorothiazide causes a marked loss of Na and of water in both fully alimented rats and in rats deprived of food and/or water. The increased urinary volume corresponds closely to the shrinkage of the extracellular fluid volume (inulin space) but the decrease in extracellular Na is not sufficient to account for the Na excretion, suggesting that Na is withdrawn from cells and perhaps bone stores as well. The fall in blood pressure in hypertensive rats is not due to simple shrinkage of the extracellular space and plasma volume, but can be referred to the rise in Na gradient induced by withdrawal of cell sodium.

Salt-Sensitivity of Volume and Blood Pressure in a Mouse with Globally Reduced ENaC γ Subunit Expression

2021 ◽  
Author(s):  
Evan C. Ray ◽  
Ashley Pitzer ◽  
Tracey Lam ◽  
Alexa Cross Jordahl ◽  
Ritam Patel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Extracellular Fluid ◽  
Body Water ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Lean Tissue ◽  
Tissue Mass ◽  
Lean Tissue Mass ◽  
Γ Subunit ◽  
Subunit Expression

The epithelial Na+ channel (ENaC) promotes the absorption of Na+ in the aldosterone-sensitive distal nephron, colon, and respiratory epithelia. Deletion of genes encoding ENaC's subunits results in early post-natal mortality. We present initial characterization of a mouse with dramatically suppressed expression of ENaC's γ subunit. We used this hypomorphic (γmt) allele to explore the importance of this subunit in homeostasis of electrolytes and body fluid volume. At baseline, γ subunit expression in γmt/mt mice was markedly suppressed in kidney and lung, while electrolytes resembled those of littermate controls. Aldosterone levels in γmt/mt mice exceeded those seen in littermate controls. Quantitative magnetic resonance (QMR) measurement of body composition revealed similar baseline body water, lean tissue mass, and fat tissue mass in γmt/mt mice and controls. γmt/mt mice exhibited a more rapid decline in body water and lean tissue mass in response to a low Na+ diet than controls. Replacement of drinking water with 2% saline selectively and transiently increased body water and lean tissue mass in γmt/mt mice, relative to controls. Lower blood pressures were variably observed in γmt/mt mice on a high salt diet, compared to controls. γmt/mt also exhibited reduced diurnal blood pressure variation, a "non-dipping" phenotype, on a high Na+ diet. While ENaC in renal tubules and colon work to prevent extracellular fluid volume depletion, our observations suggest that ENaC in other tissues may participate in regulating extracellular fluid volume and blood pressure.

scholarly journals Mechanisms of proximal tubule sodium transport regulation that link extracellular fluid volume and blood pressure

2010 ◽  
Vol 298 (4) ◽  
pp. R851-R861 ◽  
Author(s):  
Alicia A. McDonough
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Flow Rate ◽  
Sodium Transport ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
The Body ◽  
Extracellular Fluid Volume ◽  
Ang Ii ◽  
Salt Diet

One-hundred years ago, Starling articulated the interdependence of renal control of circulating blood volume and effective cardiac performance. During the past 25 years, the molecular mechanisms responsible for the interdependence of blood pressure (BP), extracellular fluid volume (ECFV), the renin-angiotensin system (RAS), and sympathetic nervous system (SNS) have begun to be revealed. These variables all converge on regulation of renal proximal tubule (PT) sodium transport. The PT reabsorbs two-thirds of the filtered Na+ and volume at baseline. This fraction is decreased when BP or perfusion pressure is increased, during a high-salt diet (elevated ECFV), and during inhibition of the production of ANG II; conversely, this fraction is increased by ANG II, SNS activation, and a low-salt diet. These variables all regulate the distribution of the Na+/H+ exchanger isoform 3 (NHE3) and the Na+-phosphate cotransporter (NaPi2), along the apical microvilli of the PT. Natriuretic stimuli provoke the dynamic redistribution of these transporters along with associated regulators, molecular motors, and cytoskeleton-associated proteins to the base of the microvilli. The lipid raft-associated NHE3 remains at the base, and the nonraft-associated NaPi2 is endocytosed, culminating in decreased Na+ transport and increased PT flow rate. Antinatriuretic stimuli return the same transporters and regulators to the body of the microvilli associated with an increase in transport activity and decrease in PT flow rate. In summary, ECFV and BP homeostasis are, at least in part, maintained by continuous and acute redistribution of transporter complexes up and down the PT microvilli, which affect regulation of PT sodium reabsorption in response to fluctuations in ECFV, BP, SNS, and RAS.

Determinants of High Blood Pressure in Salt-Deprived Renal Hypertensive Rats: Role of Changes in Plasma Volume, Extracellular Fluid Volume and Plasma Angiotensin II

1978 ◽  
Vol 55 (1) ◽  
pp. 81-87 ◽  
Author(s):  
A. J. Mourant
Keyword(s):  
Blood Pressure ◽  
Angiotensin Ii ◽  
High Blood Pressure ◽  
Plasma Volume ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Right Atrial ◽  
Free Access ◽  
Plasma Angiotensin

1. Rats with indwelling aortic and right atrial cannulae were maintained on a sodium-free diet before and after renal arterial constriction combined with contralateral nephrectomy. Control animals underwent the same protocol except that non-constricting clips were used. 2. Plasma volumes in the salt-deprived animals were lower than previously determined values in animals with free access to sodium. After clipping plasma volume increased in the hypertensive animals. Extracellular fluid volume was increased equally in both normotensive and hypertensive animals on the second postoperative day only. 3. Before clipping and contralateral nephrectomy plasma angiotensin II values were higher than normal. After the operation angiotensin II concentrations fell to normal over a period of 14 days without significant differences between experimental and control groups. 4. It is concluded that high blood pressure after clipping may be in part maintained by increases in plasma volume. However, the results strongly suggest that other renal mechanisms are likely to be of major pathogenic importance.

The Value of Plasma Renin Concentration Per Se, and in Relation to Plasma and Extracellular Fluid Volume in Diagnosis and Prognosis of Human Renovascular Hypertension

1970 ◽  
Vol 39 (5) ◽  
pp. 559-576 ◽  
Author(s):  
G. Bianchi ◽  
L. Campolo ◽  
A. Vegeto ◽  
V. Pietra ◽  
U. Piazza
Keyword(s):  
Blood Pressure ◽  
Essential Hypertension ◽  
Renal Disease ◽  
Renovascular Hypertension ◽  
Extracellular Fluid ◽  
Plasma Renin ◽  
Fluid Volume ◽  
Extracellular Fluid Volume ◽  
Plasma Renin Concentration ◽  
Diagnosis And Prognosis

1. Plasma renin concentration (PRC) has been measured in 212 hypertensive patients. In fourteen patients with essential hypertension and in seventeen patients with renovascular hypertension, plasma volume (PV) and extracellular fluid volume (ECFV) were measured. 2. The results obtained have been discussed in three ways: (a) PRC in relation to the aetiology of hypertension; (b) PRC in relation to the effect on blood pressure of surgery for unilateral renal diseases; (c) PRC, PV and ECFV in ‘essential’ and renovascular hypertension. 3. Excluding patients with ophthalmoscopic signs of malignant hypertension, PRC is significantly higher in renovascular hypertension than in normal subjects and patients suffering from ‘essential’ hypertension and hypertension associated with bilateral renal disease; but the overlapping of the single values of the patients with these diseases is marked. Thus a normal PRC has no diagnostic value, while a high PRC without sodium deficiency or retinopathy might favour a diagnosis of renovascular disease. 4. In twenty-seven out of thirty-three patients submitted to surgery for unilateral renal disease and followed up for 12 months or longer, blood pressure has been significantly reduced. This group includes twelve patients with a normal preoperative PRC and fifteen patients with a high PRC. These results clearly demonstrate that unilateral renal disease may maintain a high blood pressure without increasing PRC and that PRC has no prognostic value. 5. Concurrent estimations of PRC, PV and ECFV in patients with renovascular or essential hypertension revealed the following differences. In cases of renovascular hypertension with normal PRC, PV and ECFV were significantly increased while in those with raised PRC, PV did not differ and ECFV was barely raised with respect to values obtained in patients with essential hypertension. PV of renovascular patients with normal renin was significantly higher than that of renovascular patients with high renin. The analysis of these results with quadratic discriminant functions demonstrated that an integrated evaluation of blood pressure, PV, ECFV and PRC allows a separation between the two types of hypertension. In other words these factors, taken together, in some way seem to reflect a difference between the two diseases. These results may indicate a new type of approach to the diagnosis and prognosis of renovascular hypertension.

scholarly journals Regulation of Extracellular Fluid Volume and Blood Pressure by Pendrin

2011 ◽  
Vol 28 (3) ◽  
pp. 505-512 ◽  
Author(s):  
Juliette Hadchouel ◽  
Cara Büsst ◽  
Giuseppe Procino ◽  
Giovanna Valenti ◽  
Régine Chambrey ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Extracellular Fluid ◽  
Fluid Volume ◽  
Extracellular Fluid Volume
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