Biomedical subjects

R Franco-Saenz

Publications and source records attributed to R Franco-Saenz.

77 records · Page 5Linked to original sources

PubMedDate not supplied

Direct action of kallikrein and other proteases on the renin-angiotensin system.

Kallikrein is present in the renal tubule near the macula densa, and it has recently been shown to activate inactive renin in human plasma. We recently showed that kallikrein was a potent stimulus of renin release and increased renin secretion in a dose-dependent fashion. To study its effect on renal renin release, we superfused rat renal cortical slices with purified rat urinary kallikrein. Kallikrein-stimulated renin release was completely abolished by trasylol and by amiloride, but was not affected by soybean trypsin inhibitor. Indomethacin did not block kallikrein action, indicating that kallikrein's effect is not mediated via kinin generation and prostaglandins. Kallikrein-stimulated renin release was not blocked by propranolol, trasylol did not block isoproterenol, and dibutyryl cyclic AMP stimulated renin release, indicating that kallikrein may not play a role in the beta-adrenergic mechanism of renin release. There was no demonstrable acid-activatable or kallikrein activatable renin in the superfusate, suggesting that all of the renin release was in the active form. Cathepsin D and plasmin also stimulated renin release from kidney slices in pH 6.0 buffer, whereas trypsin and pepsin did not. Our results support the hypothesis that kallikrein may play a role in the secretion of renin by the kidney. Other proteases can also release renin from the kidney.

Angiotensins↗

PubMedDate not supplied

Effect of changes in sodium or potassium balance, and nephrectomy, on adrenal renin and aldosterone concentrations.

An active form of renin was confirmed in the adrenal gland of rats. It had a molecular weight of 40,000, generated angiotensin I (AI) from natural renin substrate at pH 7.4, and was found at concentrations 30 to 60 times higher than plasma renin in rats on a normal diet. Changes in sodium diet induced changes in adrenal capsular renin concentration (high Na 2.21 +/- 0.34, normal Na 4.34 +/- 0.53, low Na 13.19 +/- 1.67 ng AI/mg protein/hr). A high potassium diet also increased adrenal capsular renin from 5.27 +/- 0.53 to 39.78 +/- 5.68 ng AI/mg protein/hr, while plasma renin concentration decreased from 7.28 +/- 0.63 in the normal diet to 5.05 +/- 0.60 on the high potassium diet. Neither diet altered the concentration of renin in the fasciculata-medullary portion of the adrenal gland. Nephrectomy markedly increased the renin concentration in the adrenal capsules without any effect on the decapsular cells (20 hours after nephrectomy, 71.5 +/- 10.6 ng AI/mg protein/hr). Sodium loading or dexamethasone treatment prior to nephrectomy blunted the rise in adrenal renin (nephrectomy + dexamethasone = 27.64 +/- 4.33 ng AI/mg protein/hr; nephrectomy + NaCl = 38.70 +/- 5.82 ng AI/mg protein/hr). In all experiments, there was a positive correlation between adrenal renin and adrenal aldosterone concentrations, but the experiments did not rule out the possibility that this positive correlation was due to two independent variables changing in the same direction and not causally related. In conclusion, adrenal renin may be a local hormone, involved in the regulation of aldosterone production.

Adrenal Glands↗

PubMedDate not supplied

Evidence for an extrarenal source of inactive renin in rats.

We studied the source of inactive renin in plasma by investigating the changes of active and inactive renin after bilateral nephrectomy in the rat. Active renin rapidly decreased after bilateral nephrectomy, with a half-life of approximately 15 minutes. Inactive renin, on the other hand, was 20.96 +/- 1.63 ng/ml/hr before nephrectomy and gradually increased to reach a peak at 20 hours after nephrectomy (193 +/- 62 ng/ml/hr). The molecular weight of active renin was approximately 40,000 and that of inactive renin was approximately 60,000 on a Sephacryl S-200 column. Inactive renin was separated from active renin by a Cibacron blue column, and the 0 time inactive renin eluted in the same fractions as the inactive renin from 20 hours after nephrectomy. The pH optimum of inactive renin in rat renin substrate was between 5.5 and 7.5, which differs from the optimal value of pepsin or cathepsin D. The increase of inactive renin in nephrectomized rats was not prevented by removal of the salivary glands, uterus, spleen, pancreas, stomach, intestines, adrenal glands, or pituitary. In summary, inactive renin is present in the anephric rat and does not appear to be converted to active renin in the peripheral blood. The source and control of this extrarenal inactive renin are still unclear, but this renin is secreted in the rat within hours after nephrectomy.

Angiotensin I↗

PubMedDate not supplied

Effects of prostaglandin synthesis inhibitors on the renin-angiotensin system and renal function.

Equal doses (8 mg/kg) of the nonsteroidal antiinflammatory drugs indomethacin, naproxen, and sulindac and a large dose of sulindac (32 mg/kg) were administered intragastrically to conscious rats after a normal sodium diet, furosemide stimulation, and a low sodium diet for 8 days. Indomethacin, naproxen, and the high dose sulindac (32 mg/kg) decreased urinary prostaglandin E2 excretion significantly under all experimental conditions. Sulindac (8 mg/kg) suppressed prostaglandin E2 excretion after the normal and low sodium diets but not after furosemide stimulation. Indomethacin decreased plasma active renin levels under all three experimental conditions. In rats receiving a normal sodium diet, indomethacin did not affect free water clearance or renal function; however, after furosemide stimulation or a low sodium diet, indomethacin caused a significant reduction of free water clearance and glomerular filtration rate. Naproxen and sulindac (8 mg/kg) did not suppress active renin under any of the experimental conditions. However, naproxen and sulindac caused a significant reduction in free water clearance and glomerular filtration rate after furosemide stimulation and a low sodium diet. Indomethacin, naproxen, and the high dose sulindac suppressed renal prostaglandin E2 excretion under all experimental conditions. Renal prostaglandin E2 does not appear to be necessary for active renin secretion. Indomethacin is the most potent inhibitor of active renin and, therefore, most likely to cause hyporeninemia. Volume depletion appeared to sensitize the kidney to the adverse effects of nonsteroidal antiinflammatory drugs.

Aldosterone↗

PubMedDate not supplied

Localization of abnormal parathyroid tissue with use of technetium-99m-sestamibi.

OBJECTIVE: To evaluate the efficacy of "double-phase" technetium-99m-sestamibi scanning in the localization of abnormal parathyroid tissue in patients with hyperparathyroidism. METHODS: We present a prospective review of patients with hyperparathyroidism seen at a university teaching hospital between June 1994 and May 1997. Twenty-four patients entered into the study underwent preoperative localization with double-phase technetium-99m-sestamibi. The nuclear medicine results were compared with the operative findings. RESULTS: The Tc-99m-sestamibi scan correctly identified the location of single parathyroid adenomas in 22 patients (100%). Of the other two patients, both with diffuse parathyroid hyperplasia, one had a negative sestamibi scan and one had only the two inferior parathyroid glands localized on the sestamibi scan. One patient with recurrent hypercalcemia, who previously underwent total parathyroidectomy and parathyroid autotransplantation into the left forearm, had activity localized to that forearm but not to the neck. Subsequently, hyperplastic parathyroid tissue was successfully removed from the transplantation site. Another patient, who had previously undergone two unsuccessful surgical explorations prompted by hyperparathyroidism, had sestamibi localization of an adenoma inferior and medial to the right submandibular gland. The third surgical exploration disclosed a large adenoma medial to the carotid artery, just below the angle of the jaw. In two elderly, debilitated women with positive scans, adenomas were removed with use of local anesthesia. Of 22 patients in whom long-term follow-up was available, 21 remained normocalcemic for a mean period of 11.4 +/- 1.7 months postoperatively. One patient in whom hyperplastic parathyroid tissue had been removed from the left forearm had recurrence of hypercalcemia 1 year after operation. CONCLUSION: Technetium-99m-sestamibi scanning is a reliable method for identifying parathyroid adenomas but not as helpful in localizing hyperplastic parathyroid glands. The precise localization of an adenoma simplifies surgical exploration and in selected patients may allow excision of the adenoma under local anesthesia. Tc-99msestamibi scanning has become the preferred method for noninvasive localization of abnormal parathyroid glands.

Journal Article↗