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Biomedical subjects

G Onesti

Publications and source records attributed to G Onesti.

At least 19 recordsLinked to original sources

Neurogenic activity--angiotensin II interaction during the development and maintenance of renal hypertension in the rat.

1. Pentolinium tartrate (a ganglionic blocker) was injected in conscious rats during the early and late phases of two-kidney renal hypertension produced by aortic ligation. 2. In the early phase ( 5 days after aortic ligation), ganglionic blockade resulted in a decrease in blood pressure equal to that obtained in normotensive rats. Later, at days 12 and 40, for equally severe hypertension, ganglion blockade resulted in a greater decrease in blood pressure. 3. A 30 min infusion of [Sar1, Ala8]angiotensin II during the pentolinium-induced nadir in blood pressure resulted in a further decrease in blood pressure at day 5. Later, at days 12 and 40, this effect was smaller. 4. A 300 min infusion of [Sar1, Ala8]angiotensin II normalized the blood pressure in hypertensive rats at day 40. This delay response may be secondary to a central effect of the antagonist, reducing neurogenic tone or peripheral antagonism of locally generated angiotensin II in the blood vessel walls. 5. At day 40, removal of the small left kidney resulted in a greater decrease in blood pressure. This suggests the presence of a renal factor other than renin in the chronic phase of this hypertension.

Angiotensin II

[Hemodynamic effects of antihypertensive drugs].

The physiopathology of hypertension is not fully understood, though the haemodynamic pictures accompanying the various arterial forms have been established. Clinical employment of antihypertensive drugs should tend to correct these pictures and the extent to which this is true is examined in the light of the latest evidence with respect to the drugs most commonly used.

Adrenergic beta-Antagonists

Timolol kinetics in chronic renal insufficiency.

A single-dose kinetic study of oral timolol, 20 mg, was undertaken in 3 groups of volunteers with varying degrees of renal function--(1) 10 normal subjects (N); (2) 9 patients with moderate chronic renal insufficiency (MCRI; C cr, 20 to 50 ml/min); (3) 4 patients with end-stage renal disease (ESRD)--to assess the need for dosage modification as renal function diminishes. There were borderline statistical differences in absorption between groups. The mean peak concentration (C max) was 84.3 +/- 44.8 ng/ml at 0.8 +/- 0.4 hr for N and 87.1 +/- 22.8 ng/ml at 1.7 +/- 1.2 hr (p, NS) for MCRI. N and MCRI mean half-lives (5.2 +/- 2.6 hr and 4.0 +/- 1.2 hr) were not statistically different. Salivary levels correlated with plasma levels in 3 N and 1 MCRI patient. Group differences in blood pressure and pulse response to timolol seems to reflect differences present at baseline with percent change from baseline identical for the two groups except at 12 to 24 hr. Administration of timolol on an interdialysis day revealed similar kinetic and physiologic response in the normal and the MCRI group. During dialysis, timolol, 20 mg, induced significant hypotension and bradycardia.

Adult

Long-term clinical effects, bioavailability, and kinetics of minoxidil in relation to renal function.

Minoxidil was used to treat 26 patients (17 to 67 years old) with severe hypertension and varying degrees of renal function. Our object was to assess long-term clinical efficacy, kinetics (acute and chronic), and bioavailability of minoxidil in chronic renal insufficiency. Minoxidil, 27 to 30 mg per day, decreased systolic and diastolic blood pressure during the first three months of therapy. Between the third and 24th months (30 months in one patient) there was no further change. Propranolol or clonidine was needed to control heart rate, and furosemide or dialysis was needed to control edema induced by minoxidil. Renal function improved in some of the mildy azotemic patients. Minoxidil kinetics after the customary dose did not differ whether the drug was taken as tablet or solution. Kinetic parameters during chronic administration of minoxidil did not differ from those after acute administration. The kinetics in chronic renal insufficiency do not differ from these in subjects with normal renal function.

Adolescent

Effect of administration of Sar1-Ala8-angiotensin II during the development and maintenance of renal hypertension in the rat.

1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.

Angiotensin II

Effect of propranolol on blood pressure and renin in renal hypertension in the rat.

1. Propranolol was administered to groups of mature rats before and during the development of renal hypertension induced by ligation of the aorta between the renal arteries. 2. At a dose 10 mumol (3 mg) of propranolol/kg, administered by intraperitoneal injection, the onset and severity of hypertension were not affected, although plasma renin concentration was significantly lower than in the untreated hypertensive rats in the first 5 days after the operation. 3. With 200 mumol (60 mg) of propranolol/kg, administered in the drinking water, peak blood pressure 5 days after aortic ligation was lower than in the untreated control rats, but plasma renin concentration was no lower than with the smaller dose. 4. The development of severe hypertension despite reduction in plasma renin concentration on the low dose of propranolol suggests the participation of renal vasopressor factors other than renin in this model. 5. A higher dose of propranolol reduced the rise in plasma concentration to an equal extent but the rise of blood pressure at 5 days was also reduced, which supports this concept.

Animals

Pulmonary hemorrhage in renal disease: Goodpasture's syndrome and other causes.

Pulmonary hemorrhage is generally due to neoplasm, tuberculosis, necrotizing pneumonia, or bronchiectasis. If these are not found, kidney diseases, including anti-glomerular basement membrane antibody-induced bleeding (Goodpasture's syndrome), should be considered. Hemoptysis in renal disease is more often due to azotemic hypervolemia than immune reaction. Typically linear immunofluorescent patterns along the glomerular and pulmonary alveolar basement membranes must be demonstrated to confirm the diagnosis of Goodpasture's syndrome.

Adult

Salt, frusemide and renin in severe experimental renal hypertension.

1. Sodium-deficient diet failed to alter development and maintenance of severe renal hypertension produced in the rat by ligation of the aorta between the renal arteries. 2. High sodium diet did not alter the early phase of this hypertension, but significantly decreased blood pressure elevation in the late phases. 3. The decrease in blood pressure produced by high sodium intake does not appear to be mediated by renin suppression. 4. Frusemide effectively reduced blood pressure and renin at all phases.

Animals

The haemodynamic response to salt and water loading in patients with end-stage renal disease and anephric man.

1. Patients with end-stage renal disease and anephric patients underwent expansion and depletion of body fluids with salt and water. This resulted in four different sequential haemodynamic patterns: (i) no significant increase in blood pressure; (ii) increase in blood pressure associated with a rise in cardiac output and no effect on total peripheral resistance; (iii) increase in cardiac output followed by a rise in blood pressure and total peripheral resistance; (iv) increase in total peripheral resistance and blood pressure without significant changes in cardiac output. 2. It is concluded that an initial rise in cardiac output is not necessary to increase-blood pressure in either anephric man or patients with end-stage renaldisease.

Blood Pressure

The interrelation of renin and iron binding capacity.

When rats are subjected to hypoxia, an increase in serum angiotensinogen concentration occurs which is accompanied by the appearance of serum erythropoietin (EP) during the first 24 h. Subsequent increases in EP reach maximum values 24 to 48 h after increases in packed cell volume (PCV) and serum renin levels. The current experiments were designed to determine if a decrease in iron stores is the stimulus for renin production when rats are rapidly expanding their red cell volume in a hypoxic environment. Young rats fed McCall's low iron diet were paired with rats fed the same diet supplemented with ferric citrate (6 g/kg diet). After two weeks at ambient pressure, they were subjected to hypoxia (0.48 atm) for 1 to 10 days. After 5 days at the reduced pressure, a fraction of the rats on the low iron diet were fed the iron-supplemented diet. At the time of sacrifice, serum was assayed for total iron binding capacity (TIBC) and renin. Rats that were fed the low iron diet showed an increase in TIBC, an increase in serum renin and a positive correlation between serum renin and TIBC. Rats that were fed a normal iron diet under the same conditions had lower TIBC, lower serum renin and no correlation between serum renin and TIBC. When low iron diet rats were supplemented with iron, TIBC and serum renin decreased. These experiments may have a clinical counterpart. The total iron binding capacity, renin and angiotensinogen were measured in the serum of women during the first 19 weeks of pregnancy. Women during early pregnancy showed an increase in TIBC, an increase of renin and angiotensinogen in the serum and a positive correlation between TIBC and renin concentration. It is suggested that the increased concentration of renin in the serum of women during the first 19 weeks of pregnancy and in the serum of rats that are rapidly expanding their red cell volume are related to a decrease in iron stores.

Angiotensinogen

Experimental model of severe renal hypertension.

A simple technique is described for producing severe reproducible renal hypertension in the rat. Total ligation of the aorta between the renal arteries and just below the origin of the superior mesenteric artery resulted in sustained systolic and diastolic pressures in 90 per cent of 170 rats studied. Arterial pressure is then measured in the conscious unrestrained rat through a carotid cannula inserted no more than 48 hours before measurements are made. The mean arterial pressure increases to a peak of 180 mm. Hg at day 5 and then remains at a plateau of 160 mm. Hg through the 40 days of the study. Plasma renin increases to a peak at 5 days but returns to baseline at 30 days despite the persistence of severe hypertension. Infarction of the left kidney below the aortic constriction results in no increase in pressure or plasma renin. Infarctions of the right kidney by emboli originating from the indwelling carotid cannula are associated with greater increases in blood pressure and plasma renin than the standard preparation. Prolonged carotid cannulation must be avoided in order to prevent such emboli. This simple technique for producing renal hypertension allows studies on the pathogenesis of hypertension with an excellent degree of reproducibility and reliability.

Animals

Prazosin in the treatment of hypertension.

1. Prazosin decreases blood pressure in normotensive, renal hypertensive and spontaneous hypertensive rats. The effect is greatest in the last-named. 2. In spontaneously hypertensive rats the decrease in pressure is associated with a decrease in heart rate. 3. In hypertensive patients prazosin decreases blood pressure by decreasing total peripheral resistance with minor effects on cardiac output. 4. Prazosin is effective in the long-term therapy of hypertensive patients, alone and in combination with a diuretic. The effect on blood pressure is the same in the supine and standing position.

Animals