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J P Coghlan

Publications and source records attributed to J P Coghlan.

At least 19 recordsLinked to original sources
PubMed1998

Carbenoxolone does not cause a syndrome of mineralocorticoid excess in sheep.

These studies investigated whether treatment with carbenoxolone (CBX), an inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), resulted in an enhanced mineralocorticoid response to endogenous or infused cortisol. In conscious sodium replete sheep with a parotid fistula, infusion of CBX (40 mg/h for 10 days) did not increase mean arterial pressure, or change sodium and potassium status or plasma renin concentration, but significantly increased the half-life of 1,2[3H] cortisol from 18.6 +/- 4.0 to 38.8 +/- 3.9 min (p < 0.05) and reduced the blood clearance rate of cortisol (BCR) from 31 +/- 3 to 15 +/- 4 L/h (p < 0.01). The reduction in cortisol BCR was associated with reduction in cortisol secretion rate from 433 +/- 116 to 181 +/- 79 nmol/h (p < 0.01). Cortisol (8 mg/h) for 5 days increased mean arterial pressure (from 83 +/- 2 to 101 +/- 5 mmHg, p < 0.001) and caused natriuresis, hypokalaemia and hyperglycaemia. These responses were unaltered when cortisol was infused from the fifth to the tenth day of CBX infusion. These findings suggest that in sheep, carbenoxolone is either a less potent inhibitor of 11 beta-HSD2 than in other species or 11 beta-HSD2 may not be the only mechanism, which determines the specificity of the MR.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1998

An early prenatal exposure to excess glucocorticoid leads to hypertensive offspring in sheep.

1. Recent studies in animals have linked fetal exposure to excess maternal glucocorticoids with the later occurrence of cardiovascular disorders, particularly hypertension. 2. To test the hypothesis that prenatal treatment could impact on adult blood pressure two groups of pregnant ewes were transported from the farm to the Institute at either 22-29 days of pregnancy (pretreatment group 1) or 59-66 days of pregnancy (pretreatment group 2), subjected to 48 h treatment with dexamethasone (0.28 mg day-1 kg-1 for 2 days) and then returned to the farm. The control group remained at the farm for the entire pregnancy. Lambs were then studied at approximately 4, 10 and 19 months after birth. 3. The basal mean arterial pressure in pretreatment group 1 (80 +/- 1 mmHg at 124 days; 83 +/- 1 mmHg at 309 days and 89 +/- 1 mmHg at 558 days; n = 6) was significantly different (P < 0.05 in all groups) from that in the control group of lambs (74 +/- 2 mmHg at 110 days; 76 +/- 1 mmHg at 323 days and 81 +/- 1 mmHg at 568 days; n = 7). However, prenatal glucocorticoid exposure did not alter vascular sensitivity to noradrenaline, angiotensin II and adrenocorticotropic hormone in these sheep at any of the ages studied, nor did it affect basal or adrenocorticotropic hormone-induced concentrations of cortisol or basal plasma renin concentrations in the lambs at any age. 4. These data support the hypothesis that excess glucocorticoid exposure in early pregnancy, during a critical developmental stage or 'window', programmes higher blood pressure that persists in later life.

Adrenocorticotropic Hormone↗
PubMed1998

Hypothesis: aldosterone is synthesized by an alternative pathway during severe sodium depletion. 'A new wine in an old bottle'.

1. The last three steps of aldosterone biosynthesis, 11 beta-hydroxylation, 18-hydroxylation and 18-oxidation, have been demonstrated to be catalysed by one enzyme, which is the cytochrome P450(11 beta) (CYP11B) in cow, pig, sheep and bullfrog or cytochrome P450aldo (CYP11B2) in rat, human, mouse and hamster. 2. The related enzyme P450(11 beta) (CYP11B1) from rat, human, mouse and hamster adrenals displays 11 beta-hydroxylation and 18-hydroxylation activities, but not 18-oxidation activity in vitro. No such enzyme has been reported in the cow, pig or sheep to date. 3. Data showing the dissociation of aldosterone secretion from plasma angiotensin II (AngII) levels indicate the presence of other factor(s) that regulate aldosterone biosynthesis in response to changes in body sodium status. Thus, we propose the existence of a 'sodium status factor' that regulates aldosterone biosynthesis in addition to AngII, K+, adrenocorticotropic hormone and atrial natriuretic peptide. 4. We propose that during severe sodium deficiency there is a switch in the aldosterone pathway to a pathway using 18-hydroxy-deoxycorticosterone (18-OH-DOC) rather than corticosterone as an intermediate. This switch may be mediated via the putative 'sodium status factor'. 5. Two models of the hypothesis will be discussed in this paper: (i) a 'one-enzyme' model; and (ii) a 'two-enzyme' model. 6. The one-enzyme model proposes that P450aldo (P450(11 beta) as in the case of the cow, sheep and pig) changes its enzymatic activity during severe sodium deficiency (i.e. switching to the alternative aldosterone biosynthesis pathway). 7. The two-enzyme model proposes that, under normal circumstances, P450aldo synthesizes aldosterone from deoxycorticosterone, while during severe sodium deficiency the P450(11 beta) provides the substrate (i.e. 18-OH-DOC) for the P450aldo.

Aldosterone↗
PubMed1997

Effects of angiotensinogen antisense oligonucleotides on fluid intake in response to different dipsogenic stimuli in the rat.

The role of centrally synthesised angiotensinogen in neural mechanisms subserving water drinking in rats was investigated by injecting antisense oligonucleotides complementary to rat angiotensinogen mRNA into the brain with the aim of inhibiting cerebral angiotensinogen synthesis. Phosphorothioate antisense oligonucleotides (18 mer) encompassing the translation start codon were injected into the lateral ventricle of rats and their responses to a number of dipsogenic stimuli tested. These were: intracerebroventricular (i.c.v.) renin, i.c.v. angiotensin II, i.c.v. carbachol, subcutaneous isoproterenol, intravenous hypertonic saline, water deprivation for 24 h or subcutaneous injection of polyethylene glycol. Antisense treatment significantly reduced (by approximately 50%) the volume of water drunk in response to i.c.v. injection of renin or subcutaneous isoproterenol, but did not reduce water intake elicited by the other dipsogenic stimuli. The i.c.v. administration of mismatch, scrambled or sense oligonucleotides did not inhibit water intake. These data suggest that centrally produced angiotensinogen may have a role in neural pathways subserving isoproterenol-induced drinking.

Angiotensinogen↗
PubMed1997

Redistribution of carbonic anhydrase VI expression from ducts to acini during development of ovine parotid and submandibular glands.

Carbonic anhydrase VI (CA VI) is a secreted enzyme produced predominantly by serous acinar cells of submandibular and parotid glands. We have investigated the developmental pattern of CA VI production by these glands in the sheep, from fetal life to adulthood, using immunohistochemistry. Also, a specific radioimmunoassay for CA VI was used to measure changes in enzyme expression in the parotid gland postnatally. CA VI is detectable by immunohistochemistry in parotid excretory ducts from 106 days gestation (term is 145 days), in striated ducts from 138 days and in acinar cells from 1 day postnatal. The duct cell content of CA VI declined as the acinar cell population increased, a feature also of CA VI immunoreactivity in the submandibular gland. Production of CA VI by submandibular duct cells was detectable initially at 125 days gestation, and acinar production was not seen before 29 days post-natal. Apart from the differing ontogeny of CA VI production in ducts and acini of parotid and submandibular glands, there was a parallel pattern of CA VI expression during the development of these major salivary glands. With the development of the acinar tissues in the postnatal lamb, there was a dramatic increase (about 600-fold) in the level of expression of CA VI in the parotid gland between days 7 and 59 as measured by radioimmunoassay.

Animals↗
PubMed1997

Investigation of the mineralocorticoid and hypertensinogenic activity of 18-hydroxycortisol in conscious sheep.

The increased urinary excretion of 18-hydroxycortisol (18-OHF) in patients with primary aldosteronism has raised the possibility that 18-OHF is involved in the maintenance and/or pathogenesis of the associated hypertension. This study has investigated the mineralocorticoid, glucocorticoid, and hypertensinogenic activities of 18-OHF in the conscious sheep. Infusion of 18-OHF (400 micrograms/h i.v. 5 days; n = 5) alone had no effect on blood pressure or on fluid and electrolyte balance. Infusion of a combination of five adrenal steroids (aldosterone 3 micrograms/h, cortisol 5 mg/h, corticosterone 0.5 mg/h, 11-deoxycortisol 1 mg/h and deoxycorticosterone 25 micrograms/h, i.v. 5 days; n = 5) increased blood pressure by 14 +/- 1 mmHg (p < .001), but when 18-OHF was infused together with the five adrenal steroids, no additional increase in blood pressure was observed. In another group of sheep (n = 4) 18-OHF was infused at a range of doses (5, 50, 100, 200, 500, and 1000 micrograms/h i.v.), each for 2 h, into sodium-replete and sodium-deplete, adrenalectomized sheep. 18-OHF had no effect on the urinary sodium or potassium excretion or on the salivary Na/K ratio in either group as compared with vehicle infusion. To examine the renal effects of 18-OHF, a range of doses of 18-OHF (5, 50, 100, 200, 500, and 1000 micrograms/h) were infused directly into the renal artery of conscious sheep (n = 4). 18-OHF did not affect the renal blood flow nor the urinary sodium or potassium excretion compared with vehicle infusion. In summary, we could not demonstrate any mineralocorticoid, glucocorticoid, or hypertensiongenic effects of 18-OHF in conscious sheep at a dose of 400 micrograms/h. Thus, a cautious approach to interpreting the role that 18-OHF plays in the clinical manifestations of primary aldosteronism, is necessary.

Adrenalectomy↗
PubMed1997

Functional and expression analysis of ovine steroid 11 beta-hydroxylase (cytochrome P450 11 beta).

In this study, the ovine steroid 11 beta-hydroxylase (P450(11 beta) or CYP11B) cDNA previously reported by us (1) was transfected into COS-7 cells. Using 3H-11-deoxycorticosterone (3H-DOC) as the substrate, and paper partition chromatography for separation of steroid products, the expressed enzyme was shown to catalyse the conversion of DOC to corticosterone (B), 18-hydroxy-11-deoxycorticosterone (18-OH-DOC), 18-hydroxy-corticosterone (18-OH-B), and aldosterone (ALDO). These results suggest that the expressed ovine cDNA exhibited 11 beta-hydroxylase, 18-hydroxylase and aldosterone synthesis activities. The enzymatic activity of the enzyme was further analysed by adding unlabelled steroids to compete with 3H-DOC. The conversion of 3H-DOC to 3H-ALDO was inhibited by the addition of excess DOC, B and 18-OH-DOC, indicating that all these steroids were potential substrates of the enzyme. The results also demonstrated that 18-hydroxylation could occur before 11 beta-hydroxylation with this enzyme. However, the addition of excess cold 18-OH-B had no significant effect on the level of 3H-ALDO that was synthesised. This result could imply that 18-OH-B is not an intermediate involved in the conversion of DOC to aldosterone, or, more likely, the enzyme substrate site is not accessible readily. Our results also indicated that DOC was preferred to 18-OH-DOC as a substrate for the enzyme. We have demonstrated by hybridisation histochemistry using specific oligonucleotide probes that the corresponding P450(11 beta) RNA transcript was present in all zones in the sheep adrenal cortex. In summary, we have shown that the enzyme encoded by the predominant P450(11 beta) cDNA isolated from the sheep adrenocortical cDNA library has all the enzymatic activities to biosynthesise ALDO from DOC. The corresponding transcript of this ovine P450(11 beta) cDNA was located throughout the adrenal cortex and thus the inability of the zonae fasciculata-reticularis to secrete ALDO remains to be understood.

Adrenal Cortex↗
PubMed1996

The effect of relaxin on collagen metabolism in the nonpregnant rat pubic symphysis: the influence of estrogen and progesterone in regulating relaxin activity.

The aim of this study was to examine the effects of relaxin on collagen content, solubility, and composition in the rat pubic symphysis. Nonpregnant, female Sprague-Dawley rats were bilaterally ovariectomized and either unprimed or primed with estrogen or progesterone alone, or a combination of estrogen and progesterone. One week later these animals were given increasing doses of a synthetic human (gene-2) relaxin (0-100 micrograms) before being killed 16 h later. Their pubic symphysial tissues were then removed and analyzed for collagen content and solubility, whereas collagen composition was determined by SDS-PAGE. Relaxin administration significantly increased the length (140 +/- 6%) and weight (170 +/- 9%) of the interpubic fibrocartilage in estrogen-primed rats (n = 15). At the same time, it decreased the total collagen content by 68 +/- 6%, without altering the proportions of collagen types, which were predominantly type I (85%) and type II collagen (15%). Relaxin administered alone reduced the total collagen content by 64 +/- 4% but had no effect on collagen solubility or composition. Progesterone abolished the effects of relaxin in estrogen-primed rats. It is concluded that relaxin has a potent effect on the amount of collagen in the rat pubic symphysis that is enhanced by estrogen and antagonized by progesterone. The changes in the extracellular matrix within the pubic symphysis induced by relaxin may be important in the modifications that this tissue undergoes during pregnancy.

Animals↗
PubMed1996

Evidence against a central pressor mechanism for adrenocortical steroid hypertension in sheep.

The possibility that corticotropin (ACTH)-induced hypertension results from a direct central effect of the adrenocortical steroids released by ACTH was investigated in sheep. Using two approaches, steroid levels were increased in the brain while peripheral levels remained sub-pressor. The blood pressure response to intravenous infusion of a combination of 7 steroids (aldosterone, cortisol, deoxycorticosterone, corticosterone, 11-deoxycortisol, 17 alpha hydroxyprogesterone and 17 alpha 20 alpha dihydroxyprogesterone), which causes a similar pressor effect to ACTH, was compared with that caused by intracarotid infusion of the steroids at rates calculated to give concentrations in the brain equivalent to those achieved after intravenous infusion. We also examined the effects of infusing the combination of steroids directly into the central nervous system via the lateral cerebral ventricles. Intravenous infusion of the steroids increased mean arterial pressure (MAP) from a control average of 84.0 +/- 1.1mmHg to 98.2 +/- 2.2mmHg (p < 0.001) on day 5. There was no increase in MAP during intracarotid infusion, nor during intracerebroventricular infusion. These findings suggest that the adrenocortical steroids released by ACTH do not act directly on central steroid receptors to increase blood pressure.

Adrenocorticotropic Hormone↗
PubMed1995

Delta-sleep-inducing peptide sequels in the mechanisms of resistance to emotional stress.

The aim of this study is to investigate time-related changes in substance P (SP), beta-endorphin (BE), and corticosterone (CORT) levels due to DSIP aftereffects in the control and stress rats. Experiments were carried out on male Wistar and August rats. The SP and BE immunoreactivity in the hypothalamus and plasma samples was determined radioimmunologically. Blood CORT level was determined radioimmunologically. The rats were stressed at nighttime in special cages and tied by tails to the back side of the cage. The stress experiments were repeated for 12 hours for 5 days. There were 6 groups: 1. control animals, 2. stress animals, 3. rats that received DSIP in a dose of 60 nmol/kg one hour before decapitation, 4. rats in which DSIP was injected 24 hour before decapitation, 5. stressed rats in which DSIP was injected one hour before decapitation during the 5th exposure to stress, 6. stressed rats to which DSIP was injected 12 hours before the 5th exposure to stress, i.e., 24 hours before decapitation. Our experiments showed that DSIP administration induced marked changes in SP, BE, and CORT levels in hypothalamus and blood plasma. This suggests that the long-term stress-coping effect of DSIP depends on considerable changes in the level of other oligopeptides and hormones induced by DSIP. Evidently, DSIP triggers these processes inducing a cascade of interrelated molecular reactions radically different in animals with different resistance to emotional stress. This cascade of sequential reactions is different in Wistar and August rats differing by their resistance to emotional stress. DSIP administration stimulates the mechanism of resistance in August rats to a lesser extent than in Wistar animals.

Animals↗
PubMed1995

Cloning and expression analysis of a cytochrome P-450(11 beta) cDNA in sheep.

A full length ovine steroid 11 beta-hydroxylase (cytochrome P-450(11 beta)) cDNA clone from a sheep adrenal cortex cDNA library was isolated. Sequence analysis indicates that this cDNA clone resembles bovine P-450(11 beta) cDNA (95% nucleotide sequence homology) more closely than rat P-450(11 beta) cDNA (69% nucleotide sequence homology). Although the levels of nucleotide sequence homology of this cDNA clone to the rat P-450(11 beta) cDNA and the rat P-450aldo cDNA are similar, the putative amino acid sequence shows a closer resemblance to rat P-450aldo protein. Northern blot analysis shows that there are three sizes of transcript and they are expressed throughout the adrenal cortex.

Adrenal Cortex↗
PubMed1995

Pyrogenic stimulation of vascular resistance in conscious sheep.

Increased arterial blood pressure following a pyrogenic reaction has been reported in previous studies, however the mechanism of this hypertension has not been examined in detail. The present study investigated the effects of both intravenous (IV) and intracerebroventricular (ICV) injection of lipopolysaccharide (LPS) from E. coli on body temperature (Tb), mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), calculated total peripheral resistance (CTPR), stroke volume (SV) and plasma levels of adrenocorticotropin (ACTH) and arginine vasopressin (AVP) in conscious, chronically instrumented sheep. IV injection of LPS (1 microgram) increased Tb in a biphasic manner from 38.7 +/- 0.1 to 39.5 +/- 0.2 degrees C after 50 min and to 39.9 +/- 0.2 degrees C after 130 min, and MAP increased biphasically from 64 +/- 1 to 70 +/- 4 mmHg after 40 min and to 78 +/- 3 mmHg after 130 min. CO initially decreased from 4.4 +/- 0.1 to 3.5 +/- 0.1 after 40 min followed by a secondary rise to 4.8 +/- 0.1 l/min after 100 min. This occurred together with a large, biphasic increase in CTPR from 14.5 +/- 1.0 to 22.0 +/- 2.0 mmHg/l/min at 40 min, and to 18.1 +/- 0.1 mmHg/l/min at 120 min. HR increased from 68 +/- 4 to 97 +/- 4 b/min and SV decreased from 65 +/- 2 to 41 +/- 4 ml/beat during the first phase of activation. Plasma ACTH increased from 22 +/- 9 to 1043 +/- 175 pg/ml after 80 min, and plasma AVP increased from 0.7 +/- 0.2 to 12 +/- 4.0 pg/ml after 60 min. ICV injection of LPS produced a long-lasting increase in Tb and MAP, but had no effect on HR or plasma AVP. Plasma ACTH increased from 30 +/- 12 to 427 +/- 110 pg/ml. These changes suggest that intravenous pyrogenic infection produces a potent vasoconstrictor action in sheep to increase blood pressure, possibly mediated by the actions of AVP within the CNS, or other pyrogenically released vasoconstrictor factors. Furthermore, the duration of activation of the cardiovascular system following peripheral and central LPS administration is different, which together with the contrasting effects on ACTH and AVP, indicate the involvement of several hypertensive mechanisms.

Adrenocorticotropic Hormone↗
PubMed1994

Cardiovascular actions of atrial natriuretic factor in sheep with cardiac failure.

The present study examines in detail the short-term cardiovascular actions of atrial natriuretic factor (ANF) in sheep with experimental low-output cardiac failure. Five conscious sheep, surgically implanted with a ventricular pacing wire, were paced at 220 beats/min for 14 days. Most clinical symptoms of congestive heart failure (CHF) were apparent after the 14 days, characterized by low cardiac output, high venous pressure, increased total peripheral resistance, increased plasma levels of ANF, noradrenaline, arginine vasopressin and renin, and marked fluid retention. On day 14 of pacing, intravenous infusion of ANF at 100 micrograms/h for 60 min restored cardiac output to prepacing values and reduced both total peripheral resistance and right atrial pressure. These effects were sustained throughout the infusion period. No change was seen in blood pressure, plasma renin, or noradrenaline levels. These hemodynamic changes, produced by short-term infusion of ANF, contrasted with those seen in normal sheep, where there was a fall in cardiac output with increased total peripheral resistance. These changes reflect a return toward normal of the left ventricular function curve. This is the first study to report that ANF improves cardiac function in conscious sheep with CHF, primarily by a vasodilator action to reduce cardiac preload, and suggests that ANF may be useful in treating the hemodynamic effects associated with cardiac failure.

Animals↗
PubMed1994

Effects of central losartan on plasma renin and centrally mediated natriuresis.

Because intracerebroventricular (ICV) infusion of hypertonic saline or angiotensin II (Ang II) both induce water drinking, vasopressin secretion, natriuresis and increased arterial pressure, the possibility that common neural pathways mediate responses to ICV Ang II and hypertonic saline has been investigated. This was done by testing the effect of ICV infusion of the Ang II antagonist losartan on the natriuretic and pressor responses to ICV hypertonic NaCl in sheep. The effect of ICV losartan on plasma renin concentration (PRC) was also investigated. Infusion of losartan (1 mg/hr) into a lateral ventricle prevented both natriuretic and pressor responses to infusion of 0.6 mol/liter NaCl into a lateral ventricle at 1 ml/hr. In another experiment, ICV losartan at 1 mg/hr caused a pronounced increase in the PRC of Na-depleted sheep, while ICV Ang II at 3 micrograms/hr decreased PRC. The results suggest that: (i) a central angiotensinergic pathway may mediate osmoregulatory responses to centrally administered hypertonic saline, and (ii) a central angiotensinergic pathway may have a tonic inhibitory influence on renin secretion in Na-depleted animals.

Angiotensin II↗
PubMed1994

Cellular and ultrastructural location of angiotensinogen in rat and sheep kidney.

Recent evidence suggests the involvement of a local renin-angiotensin system in some renal actions of angiotensin II (Ang II). In this study the renal distribution of the precursor to angiotensin formation, angiotensinogen, was investigated in rats and sheep using immunohistochemistry, immunoelectron microscopy and non-isotopic hybridization histochemistry. Immunostaining for angiotensinogen was seen in proximal tubules (PCT) of both rat and sheep kidneys. In the rat the strongest immunostaining was found in the kidneys of neonatal (1 day old) rats. Staining declined after birth. Non-isotopic hybridization histochemistry using oligodeoxynucleotide probes labeled with biotin confirmed the presence of angiotensinogen mRNA expression in PCT of the rat renal cortex. Electron microscopic immunohistochemistry using antibodies raised against rat angiotensinogen showed weak staining in the adult of granule-like structures close to the apical membrane of PCT cells. In the neonatal rat kidney, angiotensinogen immunostaining was found throughout the PCT cells and was markedly stronger than that seen in adult rat kidney. In sheep, angiotensinogen immunostaining with an antibody raised against purified ovine angiotensinogen showed staining of PCT in fetal, newborn and adult sheep kidney. The strongest immunostaining seen was in fetal sheep kidney with a decline seen after birth. Reverse transcription polymerase chain reaction (RT-PCR) showed that angiotensinogen mRNA was expressed in the sheep kidney at all ages studied. Angiotensinogen expression was higher in fetal sheep kidneys (77 day and 141 day gestation) than in adult sheep kidney. In conclusion, angiotensinogen mRNA expression was detected in both rat and sheep kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensinogen↗
PubMed1994

Characterization of a mutant type-1 angiotensin II receptor.

We have used PCR to amplify the rat AT1 receptor from liver mRNA. The receptor DNA was subcloned into pcDNAI and a number of individual clones were transiently expressed in COS-7 cells. These individual receptors were characterized by binding of [125I] Sar1, Ile8-angiotensin II. It was found that one of the AT1 receptor clones did not bind the radiolabeled angiotensin II ligand. The mutant clone was analyzed by nucleotide sequencing. This analysis revealed that the clone has a single amino acid substitution in the third transmembrane domain of the receptor; a leucine at position 112 was changed to a proline. At this stage it is not known whether the mutant receptor is the result of a PCR artifact or an allelic difference.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1994

Cerebral osmoregulatory reduction of plasma renin concentration in sheep.

A centrally mediated inhibitory influence of plasma hypertonicity on renin secretion was investigated in conscious, Na-depleted sheep. Infusions of hypertonic solutions were made into the carotid artery or jugular vein, and the effects on plasma renin concentration (PRC) compared. Intracarotid infusion of 1.65 M NaCl significantly reduced PRC (to 74% of the pre-infusion value) within 15 min of the commencement of the infusion whereas corresponding intrajugular infusion did not. Intracarotid infusion of 3 M sorbitol for 45 min also reduced PRC (to 64% of the pre-infusion level) significantly after 15 min of infusion. By contrast, neither intrajugular infusion of 3 M sorbitol, nor intracarotid infusion of isotonic 0.15 M NaCl for 45 min significantly reduced PRC. Intracarotid infusion of hypertonic sorbitol for 45 min did not inhibit PRC in sheep with cerebral lesions of the lamina terminalis. These results show that plasma hypertonicity may have an inhibitory influence on renin secretion. The inhibition is probably mediated by an effect of hypertonicity on the CNS, rather than a direct effect on the kidney.

Animals↗