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Biomedical subjects

R Garcia

Publications and source records attributed to R Garcia.

At least 343 records · Page 19Linked to original sources

An emerging relationship between peripheral sympathetic nervous activity and atrial natriuretic factor.

The sympathetic nervous system and atrial natriuretic factor (ANF) are intimately involved in sodium, volume and blood pressure homeostasis, particularly in response to volume and pressure overloads. Although rapid progress in this field indicates several levels of interaction between both systems, the role of sympathetic nervous activity (SNA) in ANF release remains a controversial topic. There is growing evidence that ANF is an inhibitory modulator of sympathetic outflow (which in turn, may contribute to ANF's effect) and, vice-versa, SNA attenuates the target actions of ANF. Compensatory sympathetic reactions to changes induced by ANF may also have an overriding influence on its target actions. Dopamine appears to play a special role in these interactions. It is not only a precursor of norepinephrine but probably fulfills an independent function in the regulation of salt balance, similar in many respects to that of ANF.

Animals↗

Superactive analogs of the atrial natriuretic peptide (ANP).

Three analogs of the atrial natriuretic peptide ANP(105-126), lacking the N-terminal exocyclic peptide segment and containing 2-mercaptoacetic acid, 3-mercaptopropionic acid or 4-mercaptobutyric acid in place of the cysteine residue in position 105 of the peptide sequence, were synthesized by the solid-phase method. The resulting des-amino analogs showed 2 to 4 times higher diuretic/natriuretic activity than the most active natural ANP and displayed a potent hypotensive effect as well. All three analogs were relatively less potent in various in vitro bioassays and in a binding assay, indicating that their high activities in vivo may be due to resistance to enzymatic degradation and to reduced non-specific tissue adsorption. These compounds not only will serve as useful pharmacologic tools but also represent prototypes for the development of further reduced-size ANP analogs.

Adrenal Cortex↗

The propeptide Asn1-Tyr126 is the storage form of rat atrial natriuretic factor.

Granules from rat atria were isolated by differential centrifugation and by a 53% (v/v) Percoll gradient after tissue homogenization in 0.25 M-sucrose/50 mM-Na2EDTA. About 40% of the immunoreactive ANF (atrial natriuretic factor) sedimented with the atrial granules during differential centrifugations. On the Percoll gradient, two distinct bands were observed. Cell debris, mitochondria, lysosomes, myofilaments and microsomes were mostly contained in the lightest-density (rho) (1.03-1.07 g/ml) fraction, as demonstrated by electron microscopy and by enzymic markers such as lactate dehydrogenase, monoamine oxidase, cytochrome c reductase, beta-glucuronidase and acid phosphatase. Atrial granules were mostly contained in the denser (rho 1.11-1.15 g/ml) band and were only slightly contaminated by lysosomes, as shown by beta-glucuronidase activity. Analysis of the ANF content in these isolated granules by h.p.l.c., amino acid composition and sequencing demonstrated that it was only the pro-ANF [ANF-(Asn1-Tyr126)-peptide]. The precursor was present in all granules, as demonstrated by immunocytochemistry. Since hormonal propeptides usually undergo intracellular processing, and the matured peptides are subsequently stored in the secretory granules, these results indicate that the processing pathway of ANF may be different from that of other hormonal peptides.

Amino Acid Sequence↗

Relationship between age, body size, gender, and blood pressure and Doppler flow measurements in the aorta and pulmonary artery.

Previous studies have demonstrated a relationship between both age and body surface area (BSA) and M-mode echocardiographic measurements of left ventricular, left atrial, and aortic root dimensions and left ventricular wall thickness. We evaluated the relationships between age, BSA, gender and blood pressure, and Doppler aortic and pulmonary artery (PA) flow velocity measurements in 97 adults, aged 21 to 78 years, without clinical evidence of cardiac disease. No significant relationship was found between gender or blood pressure and aortic or PA flow velocity measurements. Aortic peak flow velocity, flow velocity integral, and average acceleration decreased with increasing age (all p less than 0.001), whereas ejection time (corrected for heart rate) increased, and acceleration time did not change. In contrast, there was no relationship between age and Doppler PA flow velocity measurements. Although there was no relationship between BSA and Doppler aortic flow measurements, PA peak flow velocity and average acceleration increased, while acceleration time decreased with increasing BSA (all p less than 0.02). Decreases in aortic peak flow velocity and flow velocity integral may be partly related to known increases in aortic root diameter with aging. The relationship between PA flow velocity measurements and BSA is not readily explained.

Adult↗

Immunoreactive atrial natriuretic factor is present in both atria and ventricles.

A comparative study has been made of the amount and form of immunoreactive atrial natriuretic factor (ANF) present in atria versus ventricles in situ and in cultures of atrial and ventricular cardiocytes in rats of various ages: foetus (-2 days of age), newborn (3 days of age), 10 days, 35 days and 70 days old. It was first established that ANF is present in the circulation at all ages investigated, the highest levels being found in the foetus. The atrial content of ANF increased gradually with time and was always in the microgram range. In ventricles, where it was in the nanogram range, total ANF increased with age. More ANF was found in the right than in the left atrium at all ages except in the foetus where the reverse was true. In ventricles, ANF was distributed equally between right ventricle, left ventricle and septum in the foetus, the newborn and in the adult. At 10 days and 35 days, ANF was unequally distributed: (right ventricle greater than septum greater than left ventricle). In cultured atrial cardiocytes, ANF was more abundant than in cultured ventricular cardiocytes at all ages and the amount decreased with the age of the donor animals. Atrial cardiocytes secreted more ANF than did ventricular cardiocytes at all ages investigated, the amount secreted generally decreasing with the age of the donor animals. The secretory activity of atrial cardiocytes per hour was also higher than that of their ventricular counterparts; over this time period, both types of cells secreted more ANF in the presence of serum.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

The whole heart is an endocrine gland.

The relative contribution of atria and ventricles in the release of immunoreactive (IR-) atrial natriuretic factor (ANF) and in the eventual circulating levels of the peptide was evaluated in several situations. In situ, not only atrial but also ventricular cardiocytes contain IR-ANF although the amount present in ventricles is very low, particularly in the adult rat. In cardiomyopathic hamsters with heart failure, the amount of IR-ANF decreases constantly in the atria and increases in parallel in the ventricles so that the ratio of IR-ANF which is 114:1 in control animals becomes 3.9:1 in hamsters with severe heart failure. With the Langendorff preparation, the whole heart secretes much more IR-ANF than the isolated ventricles. From the latter, IR-ANF may originate from subendocardial cells of the conduction system and, more likely, from all ventricular cardiocytes where the peptide may be secreted by two pathways: one constitutive, the other regulated. These results are in agreement with clinical studies where circulating IR-ANF was measured in the same patients following catheterization of coronary sinus and great cardiac vein (draining the left ventricle). In this situation, it was found that while the levels of IR-ANF in the great cardiac vein are higher than in the general circulation, they are much lower than in the coronary sinus. All these results tend to indicate that IR-ANF is secreted by ventricular cardiocytes in relatively low amounts even in periods of intense stimulation.

Animals↗

Cavernosography in diagnosis of metastatic tumors of the penis: 5 new cases and a review of the literature.

Secondary tumors of the penis are rare, with 266 cases having been reported. We describe 5 new cases studied by cavernosography. The primary tumors were bladder cancer in 3 patients and prostatic cancer in 2. Cavernosography suggested the diagnosis, which was confirmed by a guided biopsy or fine needle aspiration biopsy. The prognosis has been poor, with the average survival being less than 9 months.

Adenocarcinoma↗

Changes in intraocular pressure associated with the administration of propofol.

The effect of propofol on intraocular pressure (IOP) was measured in 25 patients presenting for elective non-ophthalmological surgery when propofol was used for the induction and maintenance of anaesthesia (together with 67% nitrous oxide in oxygen, and vecuronium). Normocapnia was maintained. After induction of anaesthesia, intraocular pressure was significantly lower than the baseline value; during maintenance IOP never exceeded the preinduction value. There was a temporary decrease in arterial pressure after induction. In nine patients a cutaneous flush was observed and in seven patients there was discomfort on injection. Spontaneous movement in 20% and hiccup in 12% of the patients were observed at the time of tracheal intubation.

Adult↗

Renin dependency of the effect of chronically administered atrial natriuretic factor in two-kidney, one clip rats.

Conscious two-kidney, one clip rats with 150 mm Hg or higher systolic blood pressure were infused with saralasin for 60 minutes. Those with a blood pressure decline of 30 mm Hg or more were classified as saralasin-sensitive; those with a decrease of 10 mm Hg or less were considered saralasin-resistant. The animals were then housed in metabolic cages. Groups of sham-operated normotensive, saralasin-sensitive or saralasin-resistant two-kidney, one clip (2K1C) rats were infused with atrial natriuretic factor (Arg 101-Tyr 126), 100 ng/hr per rat, for 6 days. Corresponding control groups were sham-infused. Blood pressure was initially higher in the saralasin-sensitive groups (176 +/- 6 and 181 +/- 1 mm Hg, respectively) than in the saralasin-resistant groups (160 +/- 4 and 169 +/- 4 mm Hg, respectively). Atrial natriuretic factor infusion produced a gradual decline in blood pressure to 128 +/- 5 mm Hg, but only in saralasin-sensitive 2K1C animals. Urinary volume, initially higher in saralasin-sensitive hypertensive than in normotensive rats, was depressed during atrial natriuretic factor infusion. Urinary sodium excretion and water intake showed the same tendency, but the changes were not significant. No such modifications were observed in saralasin-resistant or sham-operated rats infused with atrial natriuretic factor. Body weight, which was higher in normotensive animals, was unchanged during atrial natriuretic factor infusion. Saralasin-sensitive, noninfused 2K1C rats were the only group with higher plasma renin activity than sham-operated, normotensive controls. Plasma aldosterone was higher in the former than in the other five groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Atrial natriuretic factor during development and reversal of one-kidney, one clip hypertension.

Atrial natriuretic factor (ANF) was studied in rat plasma and atria 1, 2, 4, 6, and 8 weeks after constriction of the left renal artery and removal of the contralateral kidney. Plasma ANF was elevated at all periods of investigation. A positive correlation was observed between plasma ANF and blood pressure (r = 0.56, p less than 0.001). The total atrial ANF content (microgram/atrium) in one-kidney, one clip (1K1C) rats was lower during Weeks 1 and 2, but only in the left atrium. Lower ANF concentrations (microgram/mg protein) were also evident in the left atrium at Weeks 1, 2, and 8, and in the right atrium at Week 8. A negative correlation between ANF in plasma and in the left atrium was discerned (r = 0.43, p less than 0.01). Blood pressure (184 +/- 4 vs 114 +/- 4 mm Hg), body weight, and plasma ANF were also examined in 1K1C rats and their normotensive controls before and after unclipping. Blood pressure was normalized 6 hours after unclipping. Plasma ANF declined in 1K1C rats within 6 hours after clip removal, but it was still higher than in the controls. Plasma ANF was similar in both groups on Days 9 and 13 after unclipping. There were no differences in atrial ANF between hypertensive and normotensive animals 13 days after unclipping. The high levels of plasma ANF observed in 1K1C rats probably are secondary to increased intra-atrial pressure caused by the dual mechanism of expanded plasma volume and high blood pressure.

Animals↗

Doppler echocardiographic assessment of left ventricular systolic and diastolic function in mild hypertension.

Abnormalities in left ventricular (LV) wall thickness and mass have been demonstrated in patients with mild hypertension utilizing M-mode echocardiography. In addition, studies using radionuclide angiography have demonstrated abnormalities in early diastolic LV filling in asymptomatic hypertensive patients with normal ejection fraction and cardiac output. Recently, Doppler recordings of flow velocity in the ascending aorta and through the mitral valve have been shown to provide useful information about LV function. To determine whether flow abnormalities could be detected in patients with mild hypertension, we recorded Doppler aortic and mitral valve flow velocities in 21 men with mild hypertension. Casual systolic blood pressure was 147 +/- 18 mm Hg (mean +/- SD) and diastolic blood pressure was 96 +/- 9 mm Hg. LV mass (310 +/- 75 g) was elevated (i.e., above the 95% normal prediction interval) in 8 of 19 patients who underwent M-mode echocardiography; LV ejection fraction was normal in all patients (mean, 80%). As in previous studies in normal subjects, we found in these hypertensive patients an inverse correlation between age and both aortic peak flow velocity (r = -0.51, p less than 0.05) and transmitral early diastolic peak flow velocity (r = -0.44, p less than 0.05) and a positive relationship between age and mitral valve late diastolic peak flow velocity (r = 0.73, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Role of right and left atria in natriuresis and atrial natriuretic factor release during blood volume changes in the conscious rat.

This study investigated whether excision of either the right or left atrial appendage of rats alters their natriuretic response and the release of atrial natriuretic factor during acute blood volume expansion or reduction. These animals were subjected to a thoracotomy and either had their right or left atrial appendages removed or underwent a right or left atrial sham appendectomy for comparative, control purposes. Intrajugular vein, intracarotid artery, and intravesical catheters were installed 3-4 weeks later under sodium pentobarbital anesthesia. Then, when the rats were conscious, blood volume was expanded using blood from donor rats once every 15 minutes in 3 increments of 10% of the calculated total blood volume at a rate of 5 ml/kg/min. Blood and urine samples were collected before volume expansion and at the end of each 15-minute period, with the withdrawn blood being replaced. A maximal fourfold increase in urinary volume, urinary sodium excretion, and plasma atrial natriuretic factor was observed in all but the right-atrial-appendectomized animals. Plasma atrial natriuretic factor, urinary volume, and urinary sodium excretion were correlated in all 4 groups. No significant changes in blood pressure or hematocrit were noted. Plasma vasopressin, measured at the end of volume expansion, was significantly lower in animals subjected to left atrial appendectomy. High-performance liquid chromatography of plasma from the control groups indicated that most of the released ANF during blood volume expansion corresponded to a high molecular weight peptide. Additional rats, processed as above, were subjected to 10% blood volume decrements.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Localization of 125I-atrial natriuretic factor (ANF)-binding sites in rat renal medulla. A light and electron microscope autoradiographic study.

Using light and electron microscope autoradiography in vivo, the localization of 125I-(Arg 101-Tyr 126) atrial natriuretic factor (ANF)-binding sites was studied in the renal medulla of rats. At the light microscopic level, the autoradiographic reaction was mainly distributed in patches in the outer medulla, and followed the tubular architecture in the innermost part of the inner medulla. At the electron microscopic level, binding sites were mainly found in the outer medullary descending vasa recta and inner medullary collecting ducts. These results suggest that, in rats, the renal medulla may participate in the natriuresis and diuresis produced by ANF through vascular and tubular effects; the former by changing medullary blood flow at the level of descending vasa recta and the latter by acting on electrolyte and water transport at the level of collecting ducts.

Animals↗

Cardiac and plasma atrial natriuretic factor in experimental congestive heart failure.

The cardiac and plasma levels of immunoreactive (IR-) atrial natriuretic factor (ANF) in cardiomyopathic hamsters with moderate and severe congestive heart failure were measured, compared with those of controls, and correlated by HPLC analysis of IR-ANF in atria, ventricles, and plasma and with the ultrastructure of atrial and ventricular cells. Congestive heart failure in the hamster produced a significant increase in plasma IR-ANF, a significant decrease in atrial IR-ANF, and a marked increase in ventricular IR-ANF. The HPLC pattern of IR-ANF was of the high mol wt type in atria and ventricles of control and cardiomyopathic animals. High mol wt forms of ANF appeared in the plasma of animals with severe congestive heart failure, but not in controls. Severe congestive heart failure produced a tremendous increase in the size of the Golgi complex, with a decrease in the number and size of secretory granules in atrial cardiocytes. Ventricular cardiocytes also showed a less marked increase in the size of the Golgi complex. Secretory-like granules indistinguishable from lysosomes were present in about 1% of ventricular cardiocytes of control hamsters; in hamsters with severe congestive heart failure, secretory granules, identical to those of atrial cardiocytes, were present in greater number in about 20% of ventricular cardiocytes. Immunocytochemistry (immunogold technique) revealed that secretory granules containing IR-ANF are not present in control ventricular cardiocytes but are localized in relatively large number in about 20% of ventricular cardiocytes in hamsters with severe congestive heart failure. These results suggest that the increased IR-ANF levels (including the high mol wt forms) in animals with congestive heart failure may come from hypersecretion of both atrial and ventricular cardiocytes.

Animals↗

Body fluids and plasma atrial peptide after its chronic infusion in hypertensive rats.

To determine the role of body fluid volume in the chronic hypotensive effect of atrial natriuretic factor (ANF), spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats were infused with the peptide (Arg 101-Tyr 126) at a rate of 100 ng/h/rat for 5 days. Blood pressure (BP) was decreased from 176 +/- 4 to 133 +/- 3 mmHg in the SHR group 4 days after ANF infusion was initiated, whereas no changes were observed in ANF-infused WKY animals. Starting 5 days after the infusion began, body fluid measurements revealed no differences in plasma, blood and extracellular fluid volumes or in interstitial spaces. BP and plasma ANF concentrations were determined in another set of experiments before, during and after chronic ANF infusion. BP declined from 169 +/- 3 to 133 +/- 5 mmHg in SHR 5 days after the infusion commenced, but returned to basal values by day 10 or 11. Plasma ANF was significantly higher in SHR than in WKY rats throughout the observation period. However, there were no discernible changes in this parameter in ANF-infused SHR compared to non-infused SHR. A 3-fold rise in plasma ANF was noted in infused WKY rats at day 3 only. It is concluded that the chronic hypotensive effect of ANF in hypertensive animals is not related to changes in either body fluid volume or distribution. Moreover, the finding that chronic ANF infusion reduces BP in SHR without altering its plasma levels suggests a rapid ANF turnover.

Animals↗