Biomedical subjects

M L Blair

Publications and source records attributed to M L Blair.

At least 19 recordsLinked to original sources

PubMed2001

Parabrachial nucleus modulates cardiovascular responses to blood loss.

The goal of this study was to determine the role of the pontine lateral parabrachial nucleus (LPBN) in the compensatory responses to blood loss. Conscious unrestrained rats with complete, partial, or sham bilateral ibotenic acid lesions of the LPBN were subjected to a hypotensive 16-ml/kg blood withdrawal via arterial catheter. Complete lesions (LPBNx) encompassed the entire LPBN and extended into the ventrolateral parabrachial region to encroach on the Kolliker-Fuse nucleus. Partial lesions were restricted to the body of the LPBN and spared the outer rim of the external lateral subnucleus of the LPBN. In all three groups, serum corticosterone concentration and plasma renin activity increased four- to fivefold after hemorrhage (P < 0.01), and immunocytochemistry demonstrated numerous Fos-positive neurons in the hypothalamic supraoptic nucleus. However, the cardiovascular responses to hypotensive blood loss differed for complete and partial lesions. Blood pressure failed to recover in LPBNx rats and was significantly lower in LPBNx (66 +/- 4 mmHg) than in rats with partial or sham lesions (98 +/- 4 and 85 +/- 5 mmHg, respectively) at 40 min posthemorrhage. In contrast, rats with partial lesions had a significant attenuation of the posthemorrhage bradycardia. This implies that a population of neurons within the body of the LPBN is essential for full expression of the bradycardia that accompanies hemorrhagic hypotension, whereas the ventrolateral parabrachial region is essential for normal restoration of arterial pressure after hypotensive hemorrhage.

Animals↗

PubMed1999

Forebrain pathways mediating stress-induced hormone secretion.

Exposure to hostile conditions initiates the secretion of several hormones, including corticosterone/cortisol, catecholamines, prolactin, oxytocin, and renin, as part of the survival mechanism. Such conditions are often referred to as "stressors" and can be divided into three categories: external conditions resulting in pain or discomfort, internal homeostatic disturbances, and learned or associative responses to the perception of impending endangerment, pain, or discomfort ("psychological stress"). The hormones released in response to stressors often are referred to as "stress hormones" and their secretion is regulated by neural circuits impinging on hypothalamic neurons that are the final output toward the pituitary gland and the kidneys. This review discusses the forebrain circuits that mediate the neuroendocrine responses to stressors and emphasizes those neuroendocrine systems that have previously received little attention as stress-sensitive hormones: renin, oxytocin, and prolactin. Anxiolytic drugs of the benzodiazepine class and other drugs that affect catecholamine, GABAA, histamine, and serotonin receptors alter the neuroendocrine stress response. The effects of these drugs are discussed in relation to their effects on forebrain neural circuits that regulate stress hormone secretion. For psychological stressors such as conditioned fear, the neural circuits mediating neuroendocrine responses involve cortical activation of the basolateral amygdala, which in turn activates the central nucleus of the amygdala. The central amygdala then activates hypothalamic neurons directly, indirectly through the bed nucleus of the stria terminalis, and/or possibly via circuits involving brainstem serotonergic and catecholaminergic neurons. The renin response to psychological stress, in contrast to those of ACTH and prolactin, is not mediated by the bed nucleus of the stria terminalis and is not suppressed by benzodiazepine anxiolytics. Stressors that challenge cardiovascular homeostasis, such as hemorrhage, trigger a pattern of neuroendocrine responses that is similar to that observed in response to psychological stressors. These neuroendocrine responses are initiated by afferent signals from cardiovascular receptors which synapse in the medulla oblongata and are relayed either directly or indirectly to hypothalamic neurons controlling ACTH, prolactin, and oxytocin release. In contrast, forebrain pathways may not be essential for the renin response to hemorrhage. Thus current evidence indicates that although a diverse group of stressors initiate similar increases in ACTH, renin, prolactin, and oxytocin, the specific neural circuits and neurotransmitter systems involved in these responses differ for each neuroendocrine system and stressor category.

Animals↗

PubMed1998

Role of paraventricular nucleus parvicellular neurons in the compensatory responses to graded hemorrhage.

The goal of this study was to determine the role of the parvicellular component of the paraventricular hypothalamic nucleus (PVH) in the compensatory responses to blood loss. Male Sprague-Dawley rats were prepared with bilateral ibotenate lesions of the parvicellular PVH (PVHx; n = 5) or with sham lesions (Sham; n = 8). After >10 days recovery, hemorrhage was performed by gradual withdrawal of 16 ml/kg blood over 34 min via an indwelling femoral arterial catheter while the rats were conscious and unrestrained. Basal serum corticosterone levels, plasma renin concentration (PRC), mean arterial pressure, and heart rate did not differ between PVHx and Sham, whereas basal hematocrit was lower in PVHx than Sham (40 +/- 1 vs. 44 +/- 1; P < 0.05). After hemorrhage, corticosterone increased fourfold in Sham (P < 0.001) but did not increase significantly in PVHx. However, the blood pressure, heart rate, PRC, and hemodilution responses to hemorrhage were the same in Sham and PVHx during both the normotensive (7-13 ml/kg blood loss) and hypotensive (16 ml/kg blood loss) phases. In conclusion, the parvicellular PVH is essential for the corticosterone response, but not for the cardiovascular or renin responses to blood loss.

Animals↗

PubMed1997

Sympathetic activation cannot fully account for increased plasma renin levels during water deprivation.

This study was designed to determine if the increase in plasma renin activity (PRA) that occurs during water deprivation is mediated by the renal sympathetic nerves or adrenomedullary catecholamine release. Male Sprague-Dawley rats were studied while conscious and unrestrained. In intact or sham-operated rats, 48 h of water deprivation resulted in at least a threefold increase in PRA and plasma renin concentration (PRC) but no significant change in plasma norepinephrine or epinephrine concentration. Renal denervation decreased basal PRA, reduced the magnitude of the dehydration-induced PRA increase by 33%, and abolished the renin-suppressing effect of l-propranolol infusion in water-deprived rats. Adrenal demedullation also reduced basal and water-deprived PRA and PRC. However, even the combination of renal denervation and adrenal demedullation did not prevent a significant renin response to dehydration (control PRA of 1.8 +/- 0.6 ng x ml(-1) x h(-1) to dehydration PRA of 6.8 +/- 1.3 ng x ml(-1) x h(-1), P < 0.05). Therefore, some mechanism in addition to sympathoadrenomedullary activation plays a major role in mediating increased PRA during water deprivation.

Adrenal Medulla↗

PubMed1996

Conditioned increase in peripheral blood mononuclear cell (PBMC) number and corticosterone secretion in the rat.

Femoral artery catheters were surgically implanted into male Lewis/N rats to allow blood sampling and drug infusion in the freely moving animal. After recovery, conditioned animals received four pairings of a peppermint odor, the conditioned stimulus (CS), and an infusion of 0.1 mg/kg nicotine bitartrate, an unconditioned stimulus (US) for an increase in the number of peripheral blood mononuclear cells (PBMC) and an increase in corticosterone concentration. When reexposed to the peppermint odor, conditioned animals showed a significant increase in PBMC number and corticosterone secretion when compared to saline and unpaired control groups and previously conditioned animals that were not reexposed to the CS. Increased PBMCs were found on the fifth unreinforced CS trial. Conditioned CORT responses were lost after the initial test trial. The data indicate that the distribution of immune cells can be influenced by learning processes and support the role of learning in the regulation of corticosterone secretion.

Animals↗

PubMed1996

Role of the hypothalamic paraventricular nucleus in cardiovascular regulation.

1. The paraventricular hypothalamic nucleus (PVH) is a complex structure with both neuroendocrine and autonomic functions. It is a major source of vasopressin and the primary source of corticotropin-releasing factor. In addition, parvicellular PVH neurons have reciprocal connections with brainstem autonomic centres and directly innervate sympathetic preganglionic neurons. Evidence is reviewed which indicates that in conscious rats PVH activation increases blood pressure, heart rate, renal nerve activity and plasma renin activity. 2. In conscious rats, a non-hypotensive haemorrhage (13 mL/kg blood loss over 24 min) results in increased numbers of Fos-immunoreactive cell nuclei within both magnocellular and parvicellular PVH neurons, including the ventral medial parvicellular regions known to contain neuronal projections to brainstem autonomic centres and spinal cord sympathetic preganglionic neurons. 3. Cell-selective ibotenate lesions of the parvicellular PVH significantly blunt the corticosterone response but do not alter blood pressure, heart rate or plasma renin concentration response to non-hypotensive or hypotensive haemorrhage. This and earlier studies indicate that, while the PVH is necessary for the corticosterone response and contributes to increased vasopressin release during blood loss, it does not play an important role in the sympathetic nervous system and renin-angiotensin responses to hypovolaemia and hypotension. 4. There is evidence to indicate that the parvicellular PVH serves as a necessary relay for cardiovascular and renin responses to certain behavioural stressors. We propose that cardiovascular information relayed to parvicellular PVH autonomic regions may be used to modulate behavioural, rather than homeostatic, effects on haemodynamics and renin release.

Animals↗

PubMed1996

Female reproductive cycle influences plasma volume and protein restitution after hemorrhage in the conscious rat.

The present study was designed to test the hypothesis that gender and female reproductive cycle phase influence the restitution of blood volume following blood loss. The experiments were performed in conscious 9- to 11-wk-old Sprague-Dawley rats subjected to a slow hemorrhage of 19 ml/kg over 40 min. The effect of hemorrhage was compared in male rats and in female rats in either proestrus (Pro) or metestrus (Met). In comparison with either metestrus females or males, females hemorrhaged on the morning of proestrus showed a significantly larger overall decrease in percent hematocrit (Pro, -17 +/- 1; Met, -10 +/- 1; male, -13 +/- 1; mean +/- SE), increase in plasma volume (Pro, to 151 +/- 15% of initial volume; Met, 104 +/- 8%; male, 120 +/- 4%), and increase in total plasma protein content (Pro, to 164 +/- 14% of initial content; Met, 101 +/- 5%; male, 132 +/- 5%) over the 21-h posthemorrhage recovery period. Proestrus females also showed a larger increase in plasma osmolality during the first 2.5-h posthemorrhage than either metestrus females or males (P < 0.05). In addition, basal hematocrit and total blood volume (51Cr-tagged erythrocyte method) were higher in females studied on the morning of proestrus than in metestrus females. These results indicate that the female reproductive cycle is an important variable in basal blood volume regulation and in plasma protein and plasma volume restitution following blood loss.

Animals↗

PubMed1995

Beta-adrenergic control of renin in sodium-deprived conscious dogs: renal versus extrarenal location.

This study was designed to determine if tonic beta-adrenergic control of plasma renin activity (PRA) during dietary sodium restriction is due to stimulation of renal beta-adrenoceptors, extrarenal beta-adrenoceptors, or both. Experiments were performed in six conscious resting uninephrectomized dogs with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery. The dogs were fed a low-sodium diet of approximately 7 mequiv. Na/day. PRA decreased by 28 +/- 4% of control (p < 0.01) when the beta-adrenoceptor antagonist propranolol was infused directly into the renal artery (ira) at a rate of 0.25 micrograms.kg-1.min-1 for 45 min, whereas iv propranolol infusion at the same rate had no effect on PRA. Propranolol infusion, 1 microgram.kg-1.min-1 iv, decreased PRA by 22 +/- 8% of control (p < 0.05) and produced significantly greater systemic beta-adrenoceptor blockade but a similar renal plasma propranolol concentration as with ira infusion, 0.25 micrograms.kg-1.min-1. Thus blockade of extrarenal beta-adrenoceptors produced no additional suppression of PRA beyond that which could be accounted for by blockade of renal beta-adrenoceptors. Therefore, suppression of PRA by propranolol is due solely to blockade of renal beta-adrenergic receptors in conscious sodium-deprived dogs.

Analysis of Variance↗

PubMed1991

Dual adrenergic control of renin during nonhypotensive hemorrhage in conscious dogs.

These experiments evaluated the contribution of renal alpha-adrenoceptors, renal beta-adrenoceptors, and extrarenal beta-adrenoceptors to increased plasma renin activity (PRA) during nonhypotensive hemorrhage in conscious dogs. Blood withdrawal at a rate of 16 g/kg body wt over 20 min increased PRA to nearly threefold control levels without decreasing mean arterial pressure. The PRA response to hemorrhage was reduced to a greater extent by simultaneous direct renal arterial (ira) infusion of phenoxybenzamine and propranolol than by propranolol alone. Phenoxybenzamine infusion ira did not block alpha-adrenoceptors located outside of the kidney. The PRA and heart rate responses to hemorrhage were both significantly reduced when propranolol was infused either ira or intravenously (iv) at a rate of 2 micrograms.kg-1.min-1 for 20 min followed by 0.5 microgram.kg-1.min-1 continuous infusion. Propranolol infusion at a lower rate (0.5 microgram.kg-1.min-1 for 20 min followed by 0.12 microgram.kg-1.min-1) had little effect on the magnitude of increase in PRA when infused either iv or ira. The calculated renal arterial plasma propranolol concentration was at least fivefold higher or more during ira than during iv propranolol infusion at each rate and was approximately the same during ira infusion at the lower rate (17.5 +/- 0.7 ng/ml) as during iv infusion at the higher rate (16.7 +/- 2.4 ng/ml). These data indicate that the hemorrhage-induced increase in PRA is mediated by renal alpha-adrenoceptors and extrarenal beta-adrenoceptors, whereas renal beta-adrenoceptors appear to play little or no role.

Aldosterone↗

PubMed1990

Area postrema: essential for support of arterial pressure after hemorrhage in rats.

Previous studies have indicated that the area postrema (AP) of the rat is necessary for the development of chronic angiotensin-dependent hypertension. The present study assesses the role of the AP in the maintenance of arterial pressure during hemorrhage. Sprague-Dawley rats were given sham or AP lesions 1 wk before the experiment. They were instrumented with femoral arterial and venous catheters 2 days before the experiment. On the day of the experiment, base-line mean arterial pressure (MAP) was measured for 1 h before hemorrhage. During the following 45 min, each rat was subjected to one 7-ml/kg hemorrhage every 15 min for a total of three hemorrhages. MAP was monitored by computerized data acquisition. As shown previously, MAP was slightly but significantly lower in AP-lesion rats compared with sham-lesion rats before the hemorrhage procedure. In AP-lesion rats, hemorrhage resulted in a significantly greater fall in arterial pressure than in sham-lesion rats. In spite of larger drops in pressure in AP-lesion rats, hemorrhage caused equivalent increases in plasma renin and vasopressin in both groups. In AP-lesion rats compared with sham-lesion rats, significant bradycardia was present before hemorrhage. Hemorrhage caused bradycardia in both sham- and AP-lesion rats relative to the prehemorrhage heart rates, but AP-lesion rats showed greater bradycardia than did sham-lesion rats during every time period. We conclude that the AP may play an important role in the defense of arterial pressure against hemorrhage.

Animals↗

PubMed1989

Adrenergic control of renin during dietary sodium deprivation in conscious dogs.

These experiments evaluated the contribution of alpha- and beta-adrenergic stimulation to plasma renin activity (PRA) during early and long-term dietary sodium restriction, compared with normal sodium intake. Uninephrectomized conscious dogs with catheters in the aorta, vena cava, and remaining renal artery were studied during normal sodium diet (approximately 70 meq/day), after 2-3 days of low-sodium diet (5-7 meq/day), and after greater than or equal to 2 wk of low-sodium diet. Direct renal arterial (ira) infusion of phenoxybenzamine plus propranolol decreased PRA by similar proportions (39-48%) during all three states of dietary sodium intake. The PRA achieved after adrenergic blockade remained higher (P less than 0.05) during early and long-term sodium restriction than during normal sodium intake. The effect on PRA of ira infusion of propranolol alone was not different from that of phenoxybenzamine plus propranolol during normal or low-sodium diet, and the magnitude of decrease in PRA during low-sodium diet was the same whether propranolol (1 microgram.kg-1.min-1) was infused ira or intravenously. In summary, beta-adrenergic stimulation accounts for similar proportions of PRA during early and long-term dietary sodium restriction and during normal sodium intake. Renal alpha-adrenoceptors appear to play little or no role in control of PRA under these conditions.

Animals↗

PubMed1989

Lesion of the area postrema region attenuates hypertension in spontaneously hypertensive rats.

To determine whether the area postrema contributes to the development of hypertension in spontaneously hypertensive rats (SHR), sham or electrolytic lesions of the area postrema (AP) were made in 4-week-old SHR and Wistar-Kyoto (WKY) controls. From weeks 5 through 16, systolic pressure was measured via tail plethysmography. While blood pressure rose markedly in sham-operated SHR, increases in pressure were small in AP-ablated SHR and similar to those seen in all WKY. Subsequent direct measurements of mean arterial pressure in the same rats showed a significant correlation (r = 0.87, p less than 0.01) with the pressure data acquired via weekly tail-cuff measurement, thereby confirming that hypertension in AP-ablated SHR had indeed been attenuated. Analysis of several hundred computer-acquired measurements of mean arterial pressure from each rat showed that AP ablation shifted the distribution of mean arterial pressure to a lower range in SHR but not WKY. Ablation of the AP also decreased resting heart rate in SHR but not WKY. Suppression of heart rate in response to intravenous phenylephrine was equivalent in sham-operated and AP-ablated rats, suggesting that baroreflex-mediated slowing of heart rate was not impaired. In response to intravenous angiotensin II, suppression of heart rate was similar in sham and AP-ablated SHR, and actually was enhanced in AP-ablated WKY. Histological evaluation of the lesions indicated that visible damage to the adjacent nuclei of the solitary tracts was confined to a small portion of the commissural nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Abnormalities in hypothalamic and neurohypophysial vasopressin content are not a consequence of hypertension in the spontaneously hypertensive rat.

In order to determine if the decreased hypothalamic and increased posterior pituitary content of vasopressin (VP) observed previously in spontaneously hypertensive rats (SHR) were a secondary consequence of the hypertension, the effect of preventing the development of hypertension on VP content of the hypothalamoneurohypophyseal system was evaluated. Two methods for preventing the hypertension were used: (1) chronic angiotensin-converting enzyme inhibition (oral captopril, 100 mg/kg/day at 4-12 weeks of age); and (2) intraventricular 6-hydroxydopamine (6-OHDA, 200 micrograms at 4 and 5 weeks of age). Both of these treatments markedly attenuated the increase in systolic blood pressure in SHRs at 5-11 weeks of age. The captopril-treated rats had a significant elevation in serum renin activity at 12 weeks of age indicating the presence of chronic converting enzyme inhibition, and the 6-OHDA-treatment resulted in a depletion of hypothalamic (86%) and brainstem (76%) norepinephrine content. Hypothalamic VP content was reduced in untreated SHRs compared to normotensive Wistar-Kyoto rats (WKYs, P = 0.0015). It was not significantly altered in either strain by the 6-OHDA treatment. Captopril caused a reduction in hypothalamic VP content in both SHRs and WKYs (P less than 0.01). Posterior pituitary VP content was elevated in untreated SHRs compared to WKYs (P less than 0.001), and remained elevated with captopril and 6-OHDA treatments. These data indicate that the abnormalities in VP content in the hypothalamus and posterior pituitary of SHRs are not a response to the hypertension. Therefore, they may represent primary abnormalities in the SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Adrenergic control of renin in euhydrated and water-deprived conscious dogs.

These experiments evaluated the relative contributions of alpha- and beta-adrenoceptors to control of plasma renin activity (PRA) in conscious dogs in which PRA was elevated to two- and threefold basal levels by the orthostatic stress of passive quadruped standing and by 24-h water deprivation. All dogs were uninephrectomized and surgically prepared with chronically indwelling catheters in the aorta, vena cava, and remaining renal artery at least 10 days before experiments. Simultaneous direct renal arterial (ia) infusion of phenoxybenzamine and propranolol decreased PRA by 50% in euhydrated standing dogs and by 70% in dehydrated standing dogs without changing mean arterial pressure or heart rate. In euhydrated dogs, both ia phenoxybenzamine alone and ia propranolol alone significantly decreased PRA, but the effect of propranolol was greater than that of phenoxybenzamine. In dehydrated dogs, ia infusion of phenoxybenzamine alone did not significantly decrease PRA, whereas propranolol alone decreased PRA to nearly the same extent as combined ia alpha- and beta-adrenoceptor blockade. The majority of the adrenergically mediated component of PRA observed during orthostatic stress and dehydration in conscious dogs is therefore mediated by beta-adrenoceptors. However, PRA was similarly reduced whether propranolol was infused ia or intravenously. Thus the site of action of propranolol (intrarenal vs. extrarenal) could not be identified by these experiments.

Aldosterone↗

PubMed1988

Attenuation of spontaneous hypertension in rats by a vasopressin antagonist.

Although abnormalities in the vasopressin system have been reported in spontaneously hypertensive rats (SHR), neither short-term nor long-term administration of the vasopressin antagonist d(CH2)5-Tyr(Me)arginine vasopressin (AVP), which selectively blocks the action of vasopressin on vascular (V1) receptors, altered the course of hypertension in SHR. In the current study, long-term administration of a different vasopressin antagonist, d(CH2)5-D-Tyr(Me)VAVP, to SHR and Wistar-Kyoto rats (WKY) from 4 to 12 weeks of age significantly attenuated the development of systolic hypertension in SHR (p less than 0.05) without altering blood pressure in normotensive WKY. The antagonist was delivered subcutaneously by osmopump at 0.1 microgram/hr. Systolic blood pressure was monitored twice weekly by tail plethysmography beginning at 5 weeks of age. In a second group of SHR, the drug infusion was continued until 18 weeks of age. In this group, the attenuation of systolic hypertension by the drug was extended and became more prominent (p less than 0.007). Resting mean arterial pressure measured by indwelling catheters in the conscious state at 18 weeks of age was significantly reduced in the antagonist-treated SHR (144 +/- 4 vs 157 +/- 4 mm Hg; p less than 0.05). Heart rate also was significantly reduced by the drug (351 +/- 6 vs 392 +/- 7 beats/min; p less than 0.001). Following measurement of mean arterial pressure in the rats at 18 weeks of age, the osmopumps were removed and systolic blood pressure, mean arterial pressure, and heart rate were observed until 22 weeks of age.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1987

Effects of lesions of hypothalamic catecholamines on blood pressure, fluid balance, vasopressin and renin in the rat.

Fluid balance, systolic blood pressure (BP) and serum vasopressin (VP) and renin activity (SRA) in the basal state and in response to blood volume depletion were examined in unanesthetized rats previously given intrathecal 6-hydroxydopamine (6-OHDA) to destroy catecholaminergic (CA) input to supraoptic nucleus (SON). Sham-operated rats, unoperated ad libitum hydrated rats and rats undergoing 4 days of water deprivation served as controls. The 6-OHDA lesion resulted in adipsia, a failure to conserve administered fluids and a decrease in systolic BP. Despite decreased blood volume secondary to dehydration, and decreased systolic BP, the 6-OHDA group failed to show the expected increase in serum VP. However, when blood volume was further decreased following intraperitoneal polyethylene glycol, lesioned rats showed robust VP and SRA responses. Thus, CA input to critical target areas in the hypothalamus may be necessary for maintenance of sensitivity to stimuli that normally elicit VP release. Decreased systolic BP following 6-OHDA lesions most likely results from dehydration coupled with inadequate VP responses.

Animals↗

PubMed1987

Osmotic regulation of vasopressin and renin in spontaneously hypertensive rats.

Abnormalities in the vasopressin and renin systems have been reported in spontaneously hypertensive rats (SHR). Therefore, studies were performed to evaluate the responsiveness of these systems to changes in plasma osmolality and sodium concentration. These variables were manipulated in vivo by intraperitoneal administration of distilled water, isotonic saline, or hypertonic saline to 8- and 18-week-old SHR and normotensive Wistar-Kyoto rats (WKY). Animals were decapitated 30 minutes later, and trunk blood was collected. The hypertonic saline injections resulted in an increase in plasma osmolality and serum sodium at both ages (p less than 0.001). Serum vasopressin was higher in all groups of animals receiving hypertonic saline (1200 mosm/kg H2O; p less than 0.05), but the magnitude of increase was not significantly different in the SHR and WKY at either age. Serum renin activity was lower in SHR than in WKY following acute decreases in serum sodium at 8 weeks, but it was the same for both strains at 18 weeks. Both kidney renin content and concentration were lower in SHR than in WKY at 18 weeks but not at 8 weeks. Therefore, the suppressed renin response to acute osmotic challenge in 8-week-old SHR is not the consequence of reduced kidney renin content. The vasopressin response to osmotic stimulation also was evaluated in vitro using hypothalamoneurohypophyseal explants obtained from 5-, 8-, and 18-week-old SHR and WKY.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1987

Evidence against a pressor role for vasopressin in spontaneous hypertension.

The hypothesis that the vasoconstrictor action of vasopressin may contribute to the development of hypertension in spontaneously hypertensive rats (SHR) was tested by chronic infusion of a specific antagonist of the vascular effects of vasopressin. From 4 to 13 weeks of age, SHR and Wistar-Kyoto rats (WKY) received subcutaneously either isotonic saline or the vasopressin pressor antagonist, d(CH2)5Tyr(Me)arginine vasopressin by osmopump. Systolic blood pressure was measured by tail cuff from 5 to 11 weeks of age. In SHR, the vasopressin analogue did not alter the rate or magnitude of increase in systolic blood pressure. In WKY, systolic blood pressure in the vasopressin analogue group was slightly reduced compared with the saline infusion values until 10 weeks of age (F1, 10 = 10.18, p = 0.008). At 12 to 14 weeks of age, all animals were prepared with indwelling arterial and venous catheters. Resting mean arterial pressure was not altered significantly by the vasopressin analogue infusion in either strain, but the response to an acute vasopressin infusion of 5, 15, or 50 ng/kg body weight was markedly attenuated by the analogue treatment, indicating that plasma levels of the vasopressin analogue were sufficient to block pressor effects of endogenous vasopressin. A bolus injection of the angiotensin II converting enzyme inhibitor teprotide (SQ 20881) resulted in a decrease in mean arterial pressure (p less than 0.05) that was comparable in all groups, and serum renin concentration was not elevated in the vasopressin analogue-treated rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗