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Biomedical subjects

F V Costa

Publications and source records attributed to F V Costa.

At least 37 records · Page 2Linked to original sources

Peripheral hemodynamic and humoral effects of oral zofenopril calcium (SQ. 26,991) in patients with congestive heart failure.

In 14 patients with congestive heart failure (CHF) of various grade (NYHA class 2-4) the effects of zofenopril calcium (SQ 26,991) on blood pressure and forearm circulation were studied by venous occlusion plethysmography. Changes in plasma renin activity (PRA), aldosterone, Atrial natriuretic factor (ANF) and arginine-vasopressin (AVP) were also measured. Two hours after oral administration of 7.5 mg of zofenopril we observed a decrease in blood pressure, heart rate, and forearm vascular resistance along with an increase in venous distensibility. Zofenopril also decreased ANP levels in a manner directly related to peripheral venodilatation (r = .64; P less than .05) and modified arginine-vasopressin (AVP) proportionally to the fall in blood pressure observed in response to drug administration (%SBP/%AVP: r = .64, P less than .05; %DBP/%AVP: r = .67, P less than .05). Hemodynamic and humoral responses to zofenopril occurred without any significant unwanted adverse reaction, even in patients with greater pressor reduction. We conclude that oral acute zofenopril administration, in patients with congestive heart failure, causes an arterial and venous forearm vasodilatation which is probably involved in the acute changes in plasma levels of ANF and AVP observed after drug administration.

Administration, Oral↗

Hypolipidemic effects of long-term antihypertensive treatment with captopril. A prospective study.

In 27 hypertensive patients already receiving antihypertensive treatment and with serum total cholesterol levels between 260 and 350 mg/dl, captopril in a dosage of 50 mg twice a day was substituted for one of the drugs they were taking. Patients taking a diuretic continued the same diuretic at the same dosage. After six months of therapy that included captopril, patients resumed their former therapy. Diet and physical activity remained unchanged during the study. Biochemical and blood pressure determinations were performed before captopril was begun, after three and six months of captopril therapy, and three months after the former therapy was resumed. During the regimens that included captopril, the triglyceride value was reduced from 249 to 184 mg/dl (p less than 0.05), the total cholesterol level decreased from 287 to 237 mg/dl (p less than 0.005), and the high-density lipoprotein cholesterol value rose from 40 to 51 mg/dl (p less than 0.005). The reduction in cholesterol was unrelated to blood pressure changes or to changes in serum triglyceride, glucose, or potassium levels. Treatment regimens that included captopril also induced a greater diastolic blood pressure reduction than regimens that did not include captopril. The antihypertensive efficacy of a therapeutic regimen that includes captopril, along with its favorable effect on lipid profile, could be useful in preventing cardiovascular complications in hypertensive patients.

Captopril↗

Impaired vasodilator capacity and exaggerated pressor response to isometric exercise in subjects with family history of hypertension.

The nature of the cardiovascular response to isometric exercise is still debated. An adequate blood supply to exercising muscles at the onset of contraction seems to be an important factor controlling the extent of pressor response to isometric contraction. In comparison to normotensive subjects without familiar hypertensive history (F-), normotensive subjects with family history of hypertension (F+) have a reduced peripheral vasodilator capacity which impairs the possibility to adjust the muscular blood flow during exercise. An enhanced pressor response to handgrip test was observed in F+ and this hyperresponsivity was inversely related to the extent of forearm vasodilation capacity and largely prevented by the pretest increase of blood flow in exercising muscles. Our results suggest the importance of local vasodilating capacity as a determinant of reflex pressor response to isometric exercise.

Adult↗

Use of captopril to reduce serum lipids in hypertensive patients with hyperlipidemia.

The effects on serum lipids of substituting captopril for other antihypertensive drugs were evaluated in 24 essential hypertensives with stable hypercholesterolemia (total cholesterol 250 to 350 mg/dL). Captopril, 50 mg bid, was substituted for one of the nondiuretic drugs the patients were already taking. Patients on a diuretic continued the same diuretic at the same dosage. After 6 months of treatment including captopril, patients returned for 3 months to their previous therapeutic scheme (rechallenge). Treatment with captopril caused a reduction in total cholesterol (-18%) and triglycerides (-26%) and an increase in high-density lipoprotein (HDL) cholesterol (+27%). When patients returned to their precaptopril therapy, total and HDL cholesterol returned to precaptopril values. These effects of captopril on lipid profile of hypertensive patients with hypercholesterolemia could be important for the reduction of cardiovascular complications in treated hypertensives.

Blood Pressure↗

Importance of plasma renin activity suppression and venous distensibility on pressor and natriuretic responses to intravenous salt load in borderline hypertension.

Cardiopulmonary receptors influence renin release in a variety of physiological situations and in a fashion related to the degree of peripheral venous distensibility. We studied two groups of borderline hypertensives (BHTs) with different capacities to suppress plasma renin activity in response to saline infusion (0.20 mL/kg/per minute for 2 hours). Those BHTs with low suppressive capacity (L-supp) showed an increased venous distensibility in comparison with those with high suppressive capacity (H-supp). Saline infusion led to a significant increase in blood pressure only in L-supp BHTs, which was associated with enhanced 24-hour postloading natriuresis and raised plasma levels of an Na/K ATPase inhibitor (+12.2%). This result underlines the importance of venous distensibility as a determinant of pressor and humoral response to acute volume expansion.

Adenosine Triphosphatases↗

Characterization of a Na+/K+-ATPase inhibitor from human plasma: preliminary data.

The role of an endogenous sodium pump inhibitor in the pathogenesis of hypertension has been reported in several papers. Unfortunately, because of the unknown structure and lack of biochemical characterization, some discrepancies have arisen. In this study we report a method to obtain extracts from human plasma that are able to inhibit Na+/K+-ATPase in vitro. Preliminary characterization was carried out, which showed that the extracts are able to inhibit Na+/K+-ATPase, pNPPase, and [3H]ouabain binding to red blood cells. The enzyme inhibition is not due to vanadate, FFA, or bivalent cations, and it seems to be reversible, dose-dependent, and largely prevented in E1 conformation of the enzyme. These results seem to support the hypothesis that human plasma contains a sodium pump inhibitor with many characteristics of a "ouabainlike" compound.

Blood Chemical Analysis↗

Cellular ionic composition at the prehypertensive phase of essential hypertension.

This article reviews the data from literature regarding cell sodium and potassium content in young subjects at risk of developing essential hypertension (subjects with family history of hypertension or with borderline hypertension). The studies performed with red blood cells have produced conflicting results: approximately one-half of these studies have found an increase in intracellular Na+ in subjects with family history of hypertension (genetic normotensives) whereas the other studies found no difference. The reasons for these discrepancies are discussed. Studies with leukocytes gave more univocal results and the majority of these studies found an increase in intracellular Na+ in many genetic normotensives. These observations emphasize that it is possible to find a high intracellular Na+ in subjects with normal blood pressure. Longitudinal studies are need to clarify whether subjects with high Na+ are those who will develop hypertension. The data from our studies suggest that subjects with high Na+, even if they are normotensive, exhibit an exaggerated pressor response to mental and physical activities and that a reduction in dietary salt content produces a parallel decrease in intracellular sodium and in pressor reactivity. The data on borderline hypertension are even more scarce than those on genetic normotensives and the different classification criteria produce results which are frequently not comparable. Our studies showed that in borderline subjects not only intracellular Na+ can be increased, but also intracellular K+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Captopril and hydrochlorothiazide: rationale for their combination.

The results of controlled clinical studies have shown that about 80% of hypertensive patients have a satisfactory blood pressure reduction when treated with a combination of captopril and thiazide diuretics. The high response rate to this treatment can be explained on the basis of the mechanism of action of these drugs. In the long term, diuretics act by reducing peripheral vascular resistance. The mechanism by which they reduce peripheral vascular resistance is the subject of debate, but could be explained on the basis of cellular ionic changes. From our studies, it was observed that thiazides cause a reduction in intracellular Na+ (Nai) and in intra- and extracellular K+ (Ki, Ke). Since in many patients Ke losses are greater than Ki losses, the Ki/Ke ratio (which is directly related to membrane potential and thus to vascular tone) increases. Captopril also reduces Nai, but its effects on Ke and Ki are quite different from those of thiazides. Captopril in fact causes an increase in Ki inducing a net increase in Ki/Ke. This increase can also be observed when captopril is given in combination with thiazides. Therefore the combination of captopril and thiazides has an additive effect on Nai, and increases Ki/Ke in the vast majority of patients. The decrease in Nai probably acts by reducing membrane sensitivity to catecholamines and angiotensin, whereas the increase in Ki/Ke acts by hyperpolarizing vascular smooth muscle membrane. The combination of captopril an thiazides also has favourable metabolic effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Captopril↗

Reproducibility of pressor response to handgrip: influence of time intervals, strength and duration of exercise.

1. The reproducibility of pressor response to handgrip performed at different time intervals and with different combinations of the product duration x strength of the exercise was evaluated in 14 normotensive subjects recording blood pressure with a noninvasive automatic device. 2. Subjects underwent five consecutive tests (30% of maximal voluntary contraction x 90 s) at 30 min, and 24 h intervals and repeated the test after 12 months. Furthermore, they underwent at 24 h intervals a randomized sequence of handgrip tests whose product strength x duration was combined in order to achieve either a constant or an increasing level of exercise. 3. Blood pressure response to exercise performed at 30 min intervals was much less reproducible than that induced by handgrip performed at time intervals greater than or equal to 24 h. 4. Increasing gradually the product strength x duration of the handgrip test there was a proportional blood pressure increase, whereas when the product was maintained constant diastolic blood pressure increase was also constant and reproducible within each subject. 5. This study shows that it is possible to obtain reproducible diastolic blood pressure responses to handgrip test measuring blood pressure with a non-invasive automatic device when the tests are performed at a time interval of at least 24 h. The choice of the strength and of the duration of the exercise is very important for the reproducibility of the test.

Adult↗

Pressor response to stress and exercise in the young: intracellular ion content relationships and prognostic implications.

The relationships between intracellular Na+ (Nai) and K+ (Ki) content, blood pressure and peripheral hemodynamics were investigated in young subjects with a family history of hypertension or with borderline hypertension. A direct correlation was found between Nai and pressor response to stress and exercise; after a short-term low-salt diet a parallel decrease was found in Nai and in pressor response to provocative tests. On the contrary, Ki was inversely related to diastolic blood pressure (DBP) both a rest and during mental and physical stimulation. The mechanism by which alterations in intracellular ion content lead to hemodynamic changes may be mediated by a reduced vasodilatory capacity. In fact, during handgrip testing, the increase in forearm vascular resistance (FVR) was directly related to the Nai/Ki ratio while after the exercise, FVR decrease in subjects with normal Nai/Ki and increases in those subjects with high Nak/Ki. In borderline subjects FVR at rest was inversely related to Nai but acute salt loading causes an increase in FVR proportional to Nai. These observations suggest that in subjects with borderline hypertension FVR at rest is normal perhaps as a response to a high cardiac output; however, a further hemodynamic load (salt loading) causes an increase in FVR directly related to Nai and inversely related to Ki. The study of Nai can also give useful information about the risk of developing sustained hypertension. While no subject with borderline hypertension with normal Nai developed hypertension within five years, 31% of those subjects with high Nai developed hypertension after five years.

Adult↗

Cadralazine and chlorthalidone as a second-step drug with atenolol in hypertensive patients: differences in blood pressure control during exercise.

The long-term efficacy of a new vasodilator, cadralazine (ISF 2469), and chlorthalidone have been compared in 20 hypertensive patients not adequately controlled by atenolol. After 4 weeks of treatment with atenolol 100 mg once daily, patients whose diastolic blood pressure was greater than 95 mmHg were randomly divided into two groups to receive in addition to atenolol, either cadralazine 15 mg once daily or chlorthalidone 25 mg once daily. Both treatments were administered for 6 months. At the end of treatment with atenolol and after 3 and 6 months of combination therapy, blood pressure and heart rate were measured at rest and during bicycle exercise 24 h after the last dose. Compared to atenolol alone, both cadralazine and chlorthalidone caused a significant and similar reduction in resting blood pressure. Both groups showed an increase in diastolic blood pressure during exercise while receiving atenolol alone. The addition of chlorthalidone did not modify the pressor response to exercise, whereas patients taking cadralazine had a decrease in exercise diastolic blood pressure, which was fully evident after 6 months of therapy. The reduction in exercise diastolic blood pressure induced by cadralazine was proportional to the increase in exercise heart rate, suggesting a fall in peripheral vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Cellular and humoral factors in borderline hypertension.

In this article, we review the data about Na+ and K+ lymphocyte content in young subjects with borderline hypertension. These data indicate that many borderline subjects have an abnormally high lymphocyte Na+ content (Nai) and that their pressor response to stress and exercise is directly related to Nai. Lymphocyte K+ content (Ki) is increased in about 50% of borderline subjects. Subjects in whom Ki is high, in comparison with those having a normal Ki, have a lower Nai and lower diastolic blood pressure. This suggests that these subjects have an activation of some compensatory mechanism, possibly an increase in sodium pump function. A humoral factor causing an increase in Nai was detected not only in the plasma from essential hypertensives, but also in the plasma from borderline subjects and from normal subjects with familial hypertension having high Nai. This indirect evidence of a plasma factor impairing Na+ transport was confirmed by direct measurements of the plasma ability to inhibit Na+/K+ adenosine triphosphate. Moderate short-term dietary salt restriction reduces Nai and, proportionally, pressor response to stress. In the long-term, resting blood pressure is also reduced. Dietary K+ supplementation reduces pressor response to handgrip but not resting blood pressure. Intralymphocytic Na+ content is a good predictor of future sustained hypertension, since subjects with normal Nai do not develop hypertension within 5 years, whereas subjects with high Nai develop hypertension in 31% of cases. These subjects also have an altered pressor response to mental stress and do not respond to the low-salt diet.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗

Perception of emotions in borderline hypertensive patients and normal subjects.

The ability to recognize the facial expressions of emotions was investigated in 30 borderline hypertensive patients, 16 with high intralymphocytic sodium content (ILSC) and 14 with normal ILSC, and in 34 normotensive matched controls. To this aim, 48 slides with the facial expressions of emotions and with neutral expressions were shown to the subjects by means of a tachistoscope. Two brief questionnaires, the Affective Communication Test and the Dimensions Rating Scale, were used to assess the ability to express emotions and the intensity of emotional experience in the subjects. Results show in borderline hypertensives a difficulty in recognizing emotions, with differences between the two subgroups of patients.

Adult↗

Predictors of stable hypertension in young borderline subjects: a five-year follow-up study.

Forty-four young subjects with borderline hypertension underwent a 5-year follow-up. At the first examination their intralymphocytic Na+ (Nai) was measured before and after 1 month of a low-salt diet. Blood pressure and heart rate were recorded at rest (baseline), during mental arithmetic, and after the test (recovery). After 5 years, no subject with normal Nai developed hypertension, and, furthermore, subjects with normal Nai had no increase in blood pressure values. Thirty-one percent of subjects with high Nai developed hypertension. Subjects developing hypertension were characterized by a high pressor response to mental stress and by an increase in recovery diastolic blood pressure in comparison with baseline diastolic blood pressure. Sixty percent of the subjects whose recovery diastolic blood pressure was at least 6% higher than baseline developed hypertension. Eighty percent of subjects whose Nai was not reduced after the diet became hypertensive. Nai and diastolic blood pressure were unrelated at the first examination; however, a significant correlation was found between Nai recorded at first examination and diastolic blood pressure recorded after 5 years. It is concluded that Nai is a good predictor of future blood pressure in borderline subjects and that subjects with normal Nai have a very low risk of developing high blood pressure.

Adult↗