Visualization of [125I]ANF binding sites in rat brain by an autoradiographic technique demonstrated that these sites are highly localized in areas such as the olfactory bulb, subfornical organ, area postrema and nucleus tractus solitarius. This distribution suggests that certain cardiovascular effects of ANF could be centrally mediated and that the existence of brain ANF-related peptides should be considered. Finally, moderate densities of [125I]ANF binding sites are found in the rat and guinea pig eye while low densities are seen in pituitary and pineal gland.

Animals↗

PubMedDate not supplied

Effect of atrial natriuretic factor on plasma vasopressin in conscious rats.

An intravenous (IV) bolus injection (10 micrograms) of synthetic rat atrial natriuretic factor [ANF (Arg 101-Tyr 126)] into normal conscious Sprague-Dawley rats produced a significant decrease of plasma arginine vasopressin (AVP) while 1-, 2- and 5-micrograms doses exerted no such effect. Mean arterial blood pressure (MAP) was lowered about 15 mmHg by an IV 10 micrograms bolus injection of ANF. When plasma AVP rose significantly in rats exposed to such osmotic stimuli as 600 mM NaCl and 900 mM mannitol intraperitoneally (IP), subsequent IV injection of ANF (10 micrograms) markedly depressed this parameter. Lower doses of ANF were ineffective against 600 mM NaCl IP. The significant elevation of plasma AVP levels by hypertonic sucrose 900 mM IP was not modified by ANF (10 micrograms). Blood pressure remained unchanged after IP administration of various osmotic stimuli, except mannitol, and in all these experiments an IV bolus of ANF exerted a lowering effect on MAP. Seventy-two hr water deprivation (mixed osmotic and volume stimulus) resulted in elevated plasma AVP levels which were unaffected by an IV bolus injection of ANF at doses of 0.06-10 micrograms. Immunoreactive ANF (IR-ANF) rose in plasma to 39.3 +/- 13 ng/ml 1 min after an IV bolus injection of 10 micrograms ANF, dropping to 1.01 +/- 0.2 ng/ml after 5 min and to 0.32 +/- 0.01 ng/ml after 10 min (when ANF and AVP interactions were studied), but still remained approximately six times higher than in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Disappearance of atrial natriuretic factor from circulation in the rat.

The rate of disappearance of radioiodinated forms of 3 different atrial natriuretic factors (ANF (Ser 99-Tyr 126), ANF (Arg 101-Tyr 126), ANF (Ser 103-Tyr 126)) from circulation in the rat was studied. Before proceeding to study the half-life of these peptides, the biological activity of their cold iodinated forms was examined. Upon incorporation of iodine into the ANF molecule, there was a 2 to 5-fold loss in their binding affinities to mesenteric arteries and adrenal capsules as compared to their respective uniodinated forms. A similar loss in their potency to inhibit basal aldosterone release from adrenal zona glomerulosa cells was observed. The rate of disappearance of the radioiodinated peptides from plasma was very fast; the half-life of ANF (Ser 99-Tyr 126) was 16.8 +/- 0.9 sec. Similar values were also obtained for ANF (Arg 101-Tyr 126) and ANF (Ser 103-Tyr 126). The in vivo disappearance of ANF from plasma is probably due to the binding to receptors in the cells since in vitro incubation of ANF (Ser 99-Tyr 126) with rat plasma caused only a slight loss in its immunoreactivity in the first 5 minutes. Hepatectomy and nephrectomy did not cause any major prolongation of the disappearance rate suggesting that these two organs may not be the primary sites involved in the removal of this peptide from circulation.

Animals↗

PubMedDate not supplied

An atrial natriuretic factor-like activity in rat posterior hypophysis.

An atrial natriuretic factor-(ANF) like immunoreactivity (IR-ANF), is present in the posterior hypophysis of the rat. In order to obtain more direct information on the presence and biological activity of this new posterior hypophysis peptide, we applied a procedure similar to that described for rat atria, to extract an ANF-like material from the posterior hypophysis of the rat. An analysis of the tissue extracts by reverse-phase high performance liquid chromatography (RP-HPLC) suggested that, in this organ, the ANF-like peptides may be present in multiple forms: a low molecular weight peptide which had a RP-HPLC pattern similar to that of the synthetic rat 28 amino acid C-terminal (Ser 99-Tyr 126) ANF, and an unidentified higher molecular weight peptide. The partially purified low molecular weight peptide was found to have a potency similar to that of synthetic rat ANF in the inhibition of adrenocorticotropin-stimulated aldosterone secretion in dispersed zona glomerulosa cells, suggesting that the ANF-like peptide was biologically active. Immunohistochemical visualization of the ANF-like peptides revealed the distribution of the peptide within the posterior hypophysis. There was no immunohistochemical staining for ANF in the intermediate lobe. These results suggest the existence of biologically active ANF-like peptides within the posterior hypophysis of the rat. It is possible that these peptides may modulate locally the posterior hypophysis hormone secretion.

Adrenal Glands↗

PubMedDate not supplied

Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases.

Tonin, an esteroprotease isolated from rat submaxillary gland, is a serine protease with trypsin- and chymotrypsin-like activity. The substrate specificity of tonin shows that it differs from kallikreins and is definitely not a renin-like enzyme or an angiotensin-converting enzyme. Tonin can produce directly the vasoactive peptide angiotensin II, from angiotensin I, angiotensinogen and the synthetic tetradecapeptide substrate of renin by cleavage of a Phe-His bond. It has also been found to cleave some Phe and Arg bonds in various substrates such as beta-lipotropin (beta-LPH), adrenocorticotropin (ACTH), pro-opiomelanocortin (POMC) and substance P. Here we describe the complete amino acid sequence of rat submaxillary gland, tonin. Comparison of the sequence of 219 amino acids with other serine proteases, particularly kallikreins, gamma-subunit of nerve growth factor (NGF) and the recently described gamma-renin, reveals extensive similarities. More interestingly, it also reveals the substitution of an Asp residue always found in the serine protease active site triad (Asp, His, Ser) by a Leu residue. This unusual substitution does not seem to affect the proteolytic activity of the enzyme.

Amino Acid Sequence↗

PubMedDate not supplied

An increase in urinary catecholamines of renal origin in patients with "borderline" hypertension.

Plasma and urinary catecholamines (norepinephrine and epinephrine) and urinary dopamine excretion were studied in 45 essential hypertensive patients subdivided into borderline (labile) and stable hypertension. Borderline hypertensive patients had a higher mean fractional renal clearance of catecholamines (the clearance of catecholamines relative to creatinine clearance) than both control subjects and stable hypertensive patients. A significantly positive correlation between the renal clearance of catecholamines and urinary dopamine excretion was also found in those with borderline hypertension, but not in control subjects or those with stable hypertension. These data indicate that patients with borderline hypertension have a relatively exaggerated renal catecholamine release. They probably reflect an increased sympathetic discharge to the kidney in "borderline" hypertension, occuring to a lesser degree in stable hypertension and control subjects. Thus, urinary catecholamine measurements do not specifically reflect the level of circulating catecholamines, particularly in borderline hypertension.

Adult↗

PubMedDate not supplied

Contribution of the sympathetic nervous system to the centrally-induced pressor action of angiotensin II in rats.

1. Angiotensin II (ANG II) may increase blood pressure by central nervous system mechanisms. The involvement of the sympathetic nervous system in the centrally-induced pressor effect of ANG II in the rat was investigated. 2. Plasma noradrenaline concentrations, measured as an index of sympathetic nervous system activity, increased after intracerebroventricular (i.c.v.) injection of pressor doses of ANG II, both in normotensive and in spontaneously hypertensive rts. 3. To assess the functional significance of this, the sympathetic nervous system was inhibited by phentolamine, reserpine, and guanethidine. In phentolamine-infused rats, low doses of i.c.v. ANG II elicited a blood pressure decrease, but at maximal pressor doses, no difference between phentolamine-treated and control rats was observed. In reserpinized rats, the central pressor effect of ANG II was greater than in controls. Guanethidine pretreatment did not affect the blood pressure response to i.c.v. injected ANG II. 4. It is concluded that the central pressor effects of ANG II are accompanied by a stimulation of the sympathetic nervous system. In the rat, this stimulation may be functionally important for the initial phase of the central pressor action. This could not be established for the maximal pressor responses.

Angiotensin II↗

PubMedDate not supplied

Kinetic studies of rat renin and tonin on purified rat angiotensinogen.

Kinetic studies of highly purified rat renin and rat tonin on completely purified angiotensinogen and angiotensin-tetradecapeptide synthetic renin substrate were performed. The Michaelis-Menten constant (Km) for renin, determined at the optimum pH, was 2.8 +/- 0.03 microM for angiotensinogen and 28.8 +/- 2.69 microM for angiotensin-tetradecapeptide renin substrate. The Km of purified rat tonin was determined as 0.66 +/- 0.18 microM for angiotensinogen and 2.33 +/- 0.42 microM for angiotensin tetradecapeptide. In comparison with renin, tonin shows higher affinity with respect to angiotensinogen, but the turnover number of natural substrate molecules observed with renin (0.87 s-1) is more than 3700 times higher than that of tonin (2.3 X 10(-4) s-1). Renin shows higher affinity to angiotensin tetradecapeptide than tonin, but similar turnover numbers of 2.8 and 10.0 s-1 are observed for hydrolysis of angiotensin tetradecapeptide by renin and tonin, respectively.

Angiotensinogen↗

PubMedDate not supplied

Hyperapobetalipoproteinemia. Plasma lipoprotein responses to oral fat load.

To better define lipid transport in patients with hyperapobetalipoproteinemia (HyperapoB), the response to an oral fat load was studied in six normotriglyceridemic patients with the disorder. Plasma triglycerides; Sf greater than 400, and Sf 20 to 400 triglycerides; Sf greater than 20 B100; total HDL and HDL subfractions (HDL2 and HDL3) were measured serially for a 7-hour period after an oral fat load and changes in these parameters were compared to those observed in six normolipidemic controls. In addition, plasma triglyceride levels and HDL2 and HDL3 cholesterol were also determined in seven patients with Type IV hyperlipoproteinemia: three with normal LDL apo B levels and four with HyperapoB. When the two normotriglyceridemic groups were compared, the patients with HyperapoB had significantly higher fasting levels of SF greater than 400 lipoproteins and higher fasting VLDL and LDL levels than the normal patients. After the fat load, Sf 20 to 400 triglycerides and Sf greater than 20 B100 levels increased in both groups. Plasma triglycerides rose to a higher level in the HyperapoB patients than in the normal group, but more strikingly, remained elevated in the HyperapoB patients, an elevation due principally to a persistant increase in Sf greater than 400 triglycerides. On the other hand, HDL2 cholesterol dropped substantially in the HyperapoB patients but not in the normal patients. Finally, in the hypertriglyceridemic group, after the fat load, HDL2 cholesterol levels did not change in the patients with normal LDL apo B levels but did decrease in those with elevated plasma LDL apo B.

Adult↗

PubMedDate not supplied

Free and conjugated dopamine in pheochromocytoma, primary aldosteronism and essential hypertension.

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Free and conjugated plasma catecholamines in hypertensive patients with and without pheochromocytoma.

Explore the source record for details and available documents.

Adrenal Gland Neoplasms↗

PubMedDate not supplied

Central actions and brain receptor binding of angiotensin II: Influence of sodium intake.

The effects of dietary sodium on the central actions of angiotensin II (AII) and on 125I-AII binding to brain membranes were investigated in rats fed a low-sodium or control diet and implanted with a permanent cannula into the lateral cerebral ventricle. Blood pressure (BP) responses to AII injections intracerebroventricularly (i.v.t.) were blunted in sodium-deficient rats compared with controls. The BP increases in response to i.v.t.-injected Carbachol were the same in the two groups. In sodium-depleted rats, water intake was lower than in controls after AII given i.v.t.; higher after 1.5% NaCl i.v.t.; and unchanged after Carbachol i.v.t. The pressor response to AII given i.v.t. was higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) control rats. This hyperresponsiveness to central AII was abolished by feeding a low-sodium diet. Specific 125I-AII binding in vitro to brain membranes was consistently lower in sodium-depleted rats. The results suggest that sodium depletion modifies the central actions of AII. This may be related in part to changes in the binding properties of AII receptors in the brain.

Angiotensin II↗

PubMedDate not supplied

Metaischemic (post-Goldblatt) hypertensive vascular disease in rats.

Malignant hypertension was induced in rats by aortic ligation above the left renal artery. After 7- and 28-day periods of hypertension, the characteristics of the vascular disease were studied and the kidney below the aortic ligation was removed. The blood pressure and the vascular disease were reexamined at the end of the first and fourth weeks after nephrectomy. The evolution of the vascular disease was assessed in the contralateral kidney, in the heart, and in the superior mesentery. The results obtained allowed the following conclusions: 1) when the predominant lesions are of fibrinoid necrosis and moderate intimal hyperplasia without fibromucoid changes (initial phase), the hypertension and the hypertensive vascular disease are completely reversible after the nephrectomy; 2) when the predominant lesions are proliferative endarteritis with fibromucoid changes (chronic phase), neither the hypertension nor the vascular disease are reversible after the left nephrectomy and during the period of follow-up. Therefore, the type of vascular lesion seems to be one important determinant of the reversibility of the hypertensive process after nephrectomy.

Acute Disease↗

PubMedDate not supplied

Purification of tonin by affinity chromatography.

Tonin has been purified from rat submaxillary glands. The purification procedure included affinity chromatography on Sepharose 4B coupled to antitonin followed by DEAE chromatography and gel filtration on Sephadex G-100. Homogeneity of the purified enzyme was confirmed by Sephadex G-100 gel filtration, disc electrophoresis, and isoelectric focusing on polyacrylamide gel, immunodiffusion, and immunoelectrophoresis. The tonin was purified 11.5-fold, with 35% recovery. The purified tonin has full enzymatic or immunological activity.

Animals↗