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Biomedical subjects

W F Ganong

Publications and source records attributed to W F Ganong.

At least 19 recordsLinked to original sources
PubMed1995

Reproduction and the renin-angiotensin system.

A unique aspect of the circulating renin-angiotensin system and the many independent tissue renin-angiotensin systems is their interactions at multiple levels with reproduction. These interactions, which have received relatively little attention, include effects of estrogens and possibly androgens on hepatic and renal angiotensinogen mRNA; effects of androgens on the Ren-2 gene and salivary renin in mice; the prorenin surge that occurs with but outlasts the LH surge during the menstrual cycle; the inhibitory effects of estrogens on thirst and water intake; the tissue renin-angiotensin systems in the brain, the anterior pituitary, and the ovaries and testes, that is, in all the components of the hypothalamo-pituitary-gonadal axis; the presence of some components of the renin-angiotensin system in the uterus and the fetoplacental unit; and the possible relation of renin and angiotensin to ovulation and fetal well-being. These interactions are described and their significance considered in this short review.

Animals↗
PubMed1991

Effect of head-up tilt on vasopressin secretion and arterial pressure in anesthetized rats.

The effect of 45 or 60 degrees head-up tilt on plasma arginine vasopressin (AVP) concentration, mean arterial pressure, and heart rate was studied in inactin-anesthetized rats. In all rats, there was a fall in blood pressure that was maximal within about 20-40 s and then returned toward normal. After 45 degrees head-up tilt for 30 min, AVP was increased from 7.0 +/- 1.7 to 21.0 +/- 5.9 pg/ml. Sixty-degree head-up tilt increased AVP at 5, 15, and 30 min, respectively, from 10.6 +/- 2.9 to 22.1 +/- 4.8 pg/ml, from 10.6 +/- 2.5 to 28.5 +/- 5.3, and from 16.1 +/- 4.7 to 62.6 +/- 10.3 pg/ml. After bilateral cervical vagotomy, 60 degrees head-up tilt for 30 min increased AVP, but the change was significantly reduced compared to intact animals. Bilateral sinoaortic denervation increased basal values of AVP, and there was no further increase during tilt. Bilateral electrolytic lesions of the hypothalamic paraventricular nuclei caused only a moderate reduction in the AVP response to tilt. When the effect of endogenous angiotensin II was antagonized by saralasin or its production was blocked by enalapril, the AVP response to tilt was reduced. The mean arterial pressure fell during the 1st min, but recovered rapidly when rats treated with a V1 vasopressin receptor antagonist were tilted. The data indicate that head-up tilt increases AVP secretion in anesthetized rats, that the response is mediated by the vagus and particularly by the arterial baroreceptors, and that circulating angiotensin II contributes to the response. However, the increased circulating AVP is not necessary for the maintenance of arterial pressure.

Anesthesia↗
PubMed1991

Neuroendocrine regulation of plasma angiotensinogen.

In previous studies we found that plasma angiotensinogen levels were reduced by lesions of the hypothalamic paraventricular nuclei. To determine if the decrease was caused by decreased secretion of hormones that normally stimulate angiotensinogen secretion by the liver, we correlated the changes in plasma angiotensinogen produced by paraventricular lesions with changes in plasma LH, ACTH, and thyroid hormones; compared the changes in plasma angiotensinogen and other hormones to those produced by hypophysectomy; and determined the effects of treatment with ACTH and T4 in animals with paraventricular lesions. In male Sprague-Dawley rats, bilateral lesions destroying more than 50% of the paraventricular nuclei decreased plasma angiotensinogen to 787 +/- 52 ng angiotensin-I/ml in 7 days compared to 1576 +/- 142 ng angiotensin-I/ml in sham-operated controls. Plasma T3 and T4 were also reduced, whereas there were no statistically significant changes in plasma ACTH or LH. Hypophysectomy produced a comparable decline in plasma angiotensinogen and thyroid hormone levels. Daily administration of a single dose of ACTH had no effect on plasma angiotensinogen in rats with paraventricular lesions, but T4 treatment restored plasma angiotensinogen to normal levels. The data indicate that the decline in circulating angiotensinogen produced by lesions of the paraventricular nuclei is caused by the decrease in the secretion of thyroid hormones produced by these lesions. They also demonstrate that in addition to regulating circulating renin via the sympathetic nervous system, the brain has an effect on circulating angiotensinogen via neuroendocrine control of thyroid function.

Adrenocorticotropic Hormone↗
PubMed1991

Distribution of angiotensinogen immunoreactivity in rat anterior pituitary glands.

Angiotensin II (AII) has been previously shown to be localized in the gonadotropes of the rat anterior pituitary gland. Renin and angiotensin-converting enzyme, two enzymes that participate in the generation of AII, also have been shown to be present in gonadotropes. To determine whether angiotensinogen, the precursor to AII, is present in the same cells, we have stained rat anterior pituitary sections with an antirat angiotensinogen antiserum. Angiotensinogen staining was observed in cells that had a distinctive distribution at the periphery of the gland; the number of these cells and the intensity of the staining were increased in the pituitaries of rats that had been nephrectomized 24 hr before sacrifice. When double staining was performed, we never observed colocalization of angiotensinogen with any of the known pituitary hormones or with S100 protein. The results show that in the rat anterior pituitary gland, angiotensinogen is present, at least for the most part, in cells that are different from those containing renin, angiotensin-converting enzyme, and AII.

Angiotensin II↗
PubMed1990

Pharmacological evidence for involvement of the sympathetic nervous system in the increase in renin secretion produced by a low sodium diet in rats.

To determine the degree to which increased sympathetic activity contributes to the increase in renin secretion produced by a low sodium diet, the beta-adrenergic blocking drug propranolol or saline vehicle was injected through indwelling jugular cannulas in rats fed a normal diet and rats fed a low sodium diet for 9 days. Plasma renin activity (PRA) and plasma renin concentration (PRC) were elevated by the low sodium diet, and these values were reduced 42-45% by propranolol, although they were still higher than in the normal diet controls. Plasma corticosterone was moderately elevated in cannulated rats on regular diet, compared to decapitated controls, but corticosterone did not differ between cannulated and decapitated rats on low salt diet; propranolol reduced plasma corticosterone. However, PRA and PRC were comparable in cannulated rats and decapitated controls on both the normal and the low sodium diets, and propranolol did not produce a significant reduction in PRA and PRC in rats fed the normal diet. This indicates that the effects of propranolol on PRA and PRC in the low sodium rats were not simply due to reduction of a stress-induced increase in renin secretion. The results indicate that increased sympathetic activity makes a substantial contribution to the increase in renin secretion produced by 9 days of dietary sodium restriction.

Adrenocorticotropic Hormone↗
PubMed1990

Angiotensinogen production by rat astroglial cells in vitro and in vivo.

To investigate the production of angiotensinogen by the brain, primary cultures were prepared from the brains of one-day-old rats. Two to four weeks after plating, they were transferred to serum-free medium. The cultures, which contained approximately 15% neurons, 80% astroglia and 5% other types of cells, produced angiotensinogen at a steady rate for three to four days in serum-free medium. Cultures prepared from subcortical tissue produced more angiotensinogen than cultures prepared from cerebral cortical tissue. Angiotensinogen mRNA was also identified in those cultures. Forskolin treatment had no effect on angiotensinogen production. Astroglia-enriched cultures that contained no identifiable neurons also produced angiotensinogen and its mRNA. Astroglial cells from hypothalamus and thalamus produced more of both than astroglial cells from the cerebral cortex. In situ hybridization histochemistry on sections of the hypothalamus of adult male rats showed a diffuse distribution of cells containing angiotensinogen mRNA that was more consistent with a glial than a neuronal distribution. The data indicate that most if not all of the angiotensinogen in rat brain is produced by astrocytes.

Angiotensinogen↗
PubMed1989

Allografts of CNS tissue possess a blood-brain barrier. I. Grafts of medial preoptic area in hypogonadal mice.

This study represents the first part of a three-part investigation of blood vessels supplying CNS tissue transplanted within the brains of adult mammalian hosts. The results emphasize that blood vessels in solid CNS grafts contribute a blood-brain barrier to that of the host. Neurosecretory cells in basal forebrain grafts placed intraventricularly on the dorsal surface of the host median eminence, a neurosecretory site containing fenestrated blood vessels, do not stimulate similar blood vessels to inhabit the transplanted tissue. Solid grafts of the medial preoptic area containing neurons that synthesize and secrete gonadotropic hormone-releasing hormone (GnRH) were obtained from AKR mice and placed into the third cerebral ventricle of hypogonadal (HPG) mice genetically incapable of synthesizing GnRH. GnRH neurons in the allografts were confirmed immunohistochemically. Blood vessels supplying the host median eminence and the allograft at 10 days to 3 months post-transplantation were analyzed with peroxidase cytochemistry applied in three ways: to HPG mice injected systemically with native horseradish peroxidase; to HPG mice infused into the aorta with peroxidase subsequent to perfusion fixation; and to HPG mice brains fixed by immersion and incubated for endogenous peroxidase activity in red cells retained within blood vessels. The median eminence of the HPG mouse was innervated by GnRH neurons residing within the graft, and blood vessels traversing the median eminence-allograft interface were seen rarely. The allografts contained no fenestrated endothelia, and no extravasations of blood-borne HRP were related directly to leaky blood vessels supplying the grafted tissue. Endothelial cells throughout the CNS grafts were similar morphologically to blood-brain barrier endothelia; they were nonfenestrated, exhibited interendothelial tight junctional complexes and an endomembrane system of organelles, and they endocytosed blood-borne HRP that eventually was sequestered within dense body lysosomes. The results support the belief that blood vessels supplying CNS tissue transplanted to a host brain manifest endothelial characteristics identical to those of the tissue in normal life and to those of the host CNS.

Animals↗
PubMed1989

Renin-angiotensin system in the anterior pituitary of the rat.

In rats, angiotensin II appears to be synthesized in the anterior pituitary gland and stored in gonadotropes in the same granules as the beta-subunit of luteinizing hormone (LH). The gonadotropes also contain renin-like and angiotensin-converting enzyme-like immunoreactivity, but angiotensinogen-like immunoreactivity is found in a separate population of cells and does not colocalize with any of the known anterior pituitary hormones. This suggests that angiotensinogen shuttles to the gonadotropes in a paracrine fashion. There are angiotensin II receptors on lactotropes and corticotropes, but no definite function has been established for pituitary angiotensin II in the regulation of prolactin and adrenocorticotropic hormone.

Angiotensin II↗
PubMed1989

Lack of effect of vasopressin replacement on renin hypersecretion in Brattleboro rats.

To determine how the vasopressin deficiency in homozygous Brattleboro rats with diabetes insipidus produces increased renin secretion, homozygous and heterozygous Brattleboro rats were infused through subcutaneously implanted Alzet minipumps for 1 wk with a dose of arginine vasopressin that restored plasma vasopressin to normal in the homozygous animals. In the homozygous animals, plasma renin activity (PRA) and the PRA response to immobilization remained elevated compared with Long-Evans controls. Propranolol reduced PRA to normal and markedly reduced the PRA response to immobilization. PRA was normal in heterozygous Brattleboro rats. The data indicate that the increased renin secretion in homozygous rats is a result of increased sympathetic activity, and because circulating vasopressin does not cross the blood-brain barrier, it seems likely that the increased sympathetic activity is central in origin.

Animals↗
PubMed1989

Correlation between the stress-induced transient increase in corticotropin-releasing hormone content of the median eminence of the hypothalamus and adrenocorticotropic hormone secretion.

Intravenous angiotensin II and ether stress were found to produce a rapid, transient increase in the corticotropin-releasing hormone (CRH) content of the median eminence as measured by a radioimmunoassay employing an antibody against rat CRH(1-41). This confirms previous reports of transient increases in CRH measured by bioassay. The increase did not occur in the paraventricular region or in other parts of the brain. It occurred along with an increase in plasma adrenocorticotropic hormone (ACTH) when a second ether stress was administered 1 h after the first, and it also occurred when rats that had been adrenalectomized for 5 days were exposed to ether. The increases in CHR and the ACTH responses to ether were reduced or abolished by dexamethasone and pentobarbital. Four days after semicircular knife cuts in the posterior hypothalamus, resting CRH in the median eminence was increased but there was no further rise after ether stress. Plasma ACTH was normal at rest after the cuts, but the increase produced by ether was reduced. The ACTH responses to angiotensin II and immobilization were also reduced. Because the posterior knife cuts reduced hypothalamic catecholamine content, the effects of reducing hypothalamic norepinephrine and epinephrine by administration of the dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDC) were tested. Five hours after DDC, plasma ACTH was elevated but there was no further increase with ether stress. The median eminence CRH content was normal but failed to increase after exposure to ether.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Angiotensin II in the brain and pituitary: contrasting roles in the regulation of adenohypophyseal secretion.

Angiotensin II (AII) is present in gonadotropes in rats, and there are AII receptors on lactotropes and corticotropes. AII may be a paracrine mediator that stimulates the secretion of prolactin and adrenocorticotropin (ACTH) at the level of the pituitary, but additional research is needed to define its exact role. Angiotensinogen may also reach the gonadotropes via a paracrine route. On the other hand, there is considerable evidence that brain AII stimulates the secretion of luteinizing hormone (LH) by increasing the secretion of LH-releasing hormone, and that this effect is due to AII-mediated release of norepinephrine from noradrenergic nerve terminals in the preoptic region of the hypothalamus. In addition, brain AII inhibits the secretion of prolactin, probably by increasing the release of dopamine into the portal hypophyseal vessels. Circulating AII stimulates the secretion of a third anterior pituitary hormone, ACTH, by acting on one or more of the circumventricular organs to increase the secretion of corticotropin-releasing hormone.

Angiotensin II↗
PubMed1988

Pharmacological evidence that the sympathetic nervous system mediates the increase in renin secretion produced by immobilization and head-up tilt in rats.

To determine the mechanism by which immobilization and head-up tilt under inactin anesthesia increase plasma renin activity (PRA), the effect of these stimuli on plasma levels of vasoactive intestinal polypeptide (VIP) were measured and the effect of the beta-adrenergic blocking drug, propranolol on the response of plasma renin activity determined. Increases in circulating VIP are known to stimulate secretion of renin. After 10 min of immobilization, plasma renin activity was increased and VIP in plasma was unchanged. After 30 min of tilting, plasma renin activity was also increased and VIP in plasma was unchanged. The increases in plasma renin activity were blocked by propranolol. Inactin anesthesia by itself increased plasma renin activity and this response was unaffected by propranolol and associated with a small decrease, rather than an increase in VIP in plasma. The results indicate that the responses of plasma renin activity to immobilization and head-up tilt are due to increased secretion of renin mediated by the sympathetic nervous system. On the other hand, the increase in secretion of renin produced by inactin anesthesia does not appear to be mediated by the sympathetic nervous system. There was no evidence that VIP was responsible for any of the increases.

Animals↗
PubMed1988

Vasoactive intestinal peptide and renin secretion.

VIP has now been shown to produce an increase in renin release in a number of species, including humans. Our work suggests that VIP is capable of producing this effect by a direct action on the renin-secreting juxtaglomerular cells of the kidney. We have found no evidence to support the possibility that VIP produces this effect as a neurotransmitter in the kidney. In this regard, it should be noted that VIP has been identified as a cotransmitter primarily in cholinergic neurons. The kidney is thought to lack cholinergic innervation, and acetylcholine has no effect on renin secretion. We have explored two conditions where renin secretion is known to increase and found that circulating levels of VIP did not increase along with the increase in PRA. Thus, at least in hemorrhage and dietary sodium restriction, VIP does not appear to affect renin secretion through a humoral mechanism. There could be other untested situations where a humoral effect of VIP might come into play since we have shown that the whole animal is capable of increasing plasma VIP to levels that affect renin release. Studies employing recently developed VIP antagonists have the potential to determine in which physiological or pathological situations VIP contributes to the control of renin secretion. For example, in endotoxic shock, plasma levels of both VIP and PRA are significantly elevated. Could the increase in PRA be partly dependent on an action of circulating VIP?

Animals↗
PubMed1988

Relation of the ventromedial nuclei of the hypothalamus to the regulation of renin secretion.

During an investigation of the role of the mediobasal hypothalamus in the regulation of renin secretion from the kidneys, we found that lesions of the ventromedial nuclei prevented the increase in plasma renin activity produced by p-chloroamphetamine. In the present study, we tested the effects of bilateral electrolytic lesions of the ventromedial nuclei on the increase in plasma renin activity produced in sham-operated rats by immobilization, head-up tilt under inactin anesthesia, and a low-sodium diet. Ventromedial lesions reduced or abolished the plasma renin activity increase to all three stimuli without any change in plasma angiotensinogen. The plasma renin concentration responses to immobilization and a low-sodium diet were also reduced. All these stimuli probably exert their effect by way of the sympathetic nervous system. The data support the hypothesis that the ventromedial nuclei or neural fibers passing through them are important in the renin response to diverse stimuli that act by way of sympathetic discharge.

Angiotensinogen↗
PubMed1987

The role of angiotensin II in the regulation of ACTH secretion.

1. In rats and in at least some other species, IV and IVT AII stimulate ACTH secretion. 2. Although AII increases ACTH secretion by a direct action on pituitary cells in vitro, it appears to act instead by stimulating CRH secretion in vivo. 3. The CRH stimulating effect of circulating AII is mediated by an action of the AII on one or more of the circumventricular organs of the brain. 4. AII administered into the cerebral ventricles and, presumably, centrally generated AII, increase CRH secretion by acting on AII receptors inside the blood-brain barrier as well as in the circumventricular organs. 5. A possible role for the renin-angiotensin system in mediating the increase in ACTH secretion produced by stress has been suggested, and the degree of involvement may vary from one stress to another. However, as yet we have been unable to obtain any evidence that either circulating AII or centrally generated AII plays a role in the increase in ACTH secretion produced by ether stress in rats and surgical stress in dogs.

Adrenocorticotropic Hormone↗
PubMed1987

Role of brain serotonergic pathways and hypothalamus in regulation of renin secretion.

To investigate the role of brain serotonergic neurons in the regulation of renin secretion, we measured changes in plasma renin activity (PRA), and, in some instances, plasma renin concentration (PRC), plasma angiotensinogen, and plasma adrenocorticotropic hormone (ACTH) in rats with lesions of the dorsal raphe nucleus and lesions of the paraventricular nuclei, dorsomedial nuclei, and ventromedial nuclei of the hypothalamus. We also investigated the effects of p-chloroamphetamine (PCA), immobilization, head-up tilt, and a low-sodium diet in the rats with dorsal raphe, paraventricular, and dorsomedial lesions. Lesions of the dorsal raphe nucleus abolished the increase in PRA produced by PCA but had no effect on the increase produced by immobilization, head-up tilt, and a low-sodium diet. Paraventricular lesions, which abolish the increase in plasma ACTH produced by PCA, immobilization, and head-up tilt, decreased plasma angiotensinogen. The paraventricular lesions abolished the PRA and the PRC responses to PCA and the PRA but not PRC response to immobilization, head-up tilt, and a low-sodium diet. The ventromedial lesions abolished the PRA and PRC responses to PCA and did not reduce plasma angiotensinogen. The data suggest that paraventricular lesions depress angiotensinogen production by the liver and that the paraventricular and ventromedial nuclei are part of the pathway by which serotonergic discharges increase renin secretion. They also suggest that the serotonergic pathway does mediate the increases in renin secretion produced by immobilization, head-up tilt, and a low-sodium diet.

Animals↗