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T Bennett

Publications and source records attributed to T Bennett.

At least 145 records · Page 8Linked to original sources
PubMed1993

Structure and functional expression of a complementary DNA for porcine growth hormone-releasing hormone receptor.

Growth hormone-releasing hormone (GHRH) belongs to the family of gut-neuropeptide hormones which also includes glucagon, secretin and vasoactive intestinal peptide (VIP). All receptors for this peptide hormone family seem to involve similar signal transduction pathways. Upon hormone binding, these receptors interact with guanine nucleotide binding protein 'Gs' and cause the stimulation of adenylate cyclase. The secretin and VIP receptor cDNAs have recently been cloned and found to be homologous to those of calcitonin and parathyroid hormone receptors. Based on cDNA sequences of these receptors, we designed several oligonucleotide primers which were used to amplify two novel porcine pituitary cDNA fragments by the polymerase chain reaction. One novel receptor cDNA fragment was used to screen a porcine pituitary cDNA library and a full-length cDNA encoding a putative porcine GHRH receptor of 451 amino acids was isolated. This putative receptor mRNA is present specifically in porcine anterior pituitary cells and not in eight other porcine tissues as shown by Northern hybridization analysis. The receptor cDNA was subsequently cloned into a mammalian cell expression vector containing the cytomegalovirus promoter. A human kidney tumor cell line (293) stably transfected with this vector was found to express the receptor efficiently and to bind [125I]-GHRH specifically. Furthermore, challenge of the 293 cells expressing the receptor by GHRH leads to efficient stimulation of cytoplasmic cAMP production.

Amino Acid Sequence↗
PubMed1993

Magnesium sulphate reverses the carotid vasoconstriction caused by endothelin-I, angiotensin II and neuropeptide-Y, but not that caused by NG-nitro-L-arginine methyl ester, in conscious rats.

1. Magnesium sulphate (MgSO4) has been used for many years in the prevention of eclamptic seizures, but its mechanism of action has never been elucidated. Recent studies suggest that cerebral vasospasm is an important feature of eclampsia and we have developed and tested the hypothesis that MgSO4 can reverse cerebral vasoconstriction. 2. Studies were performed in conscious, male Long Evans rats with pulsed Doppler probes sutured around both common carotid arteries after the external carotid artery had been ligated on the left, thus allowing simultaneous measurement of changes in common and internal carotid blood flow. Intravascular catheters were placed in the abdominal aorta for measurement of systemic blood pressure and in the right jugular vein for administration of drugs. Mean arterial blood pressure and mean Doppler shift signals were used to calculate percentage changes in common and internal carotid vascular conductance. 3. After a period of recovery the animals were infused with endothelin-1, angiotensin II, neuropeptide-Y or NG-nitro-L-arginine methyl ester alone or in combination, and MgSO4 in low or high dose was infused when the effects of the vasoconstrictors had become established. 4. MgSO4 itself, at the low dose, had no effect on carotid vascular conductance. Endothelin-1, angiotensin II and neuropeptide-Y all reduced common and internal carotid vascular conductance and this effect was significantly attenuated by low dose MgSO4. The carotid vasoconstrictor action of endothelin-1 was completely abolished by high dose MgSO4.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Comparison of the regional haemodynamic effects of the AT1-receptor antagonists, losartan and EXP 3174, in water-deprived Brattleboro rats.

1. Two separate groups (n = 8) of Brattleboro rats, chronically instrumented for the measurement of regional haemodynamics, underwent a 2-stage experimental protocol. Initially, animals had their drinking water removed and cardiovascular recordings were made every 30 min for the following 6 h. Then animals received either the AT1-receptor antagonist, losartan (3 mg kg-1, i.v., n = 8), or an initially equi-hypotensive dose of its active metabolite, EXP 3174 (1 mg kg-1, i.v., n = 8), and the resultant cardiovascular changes were monitored for a further 2 h. A third group of Brattleboro rats (n = 8) was water-deprived for 8 h to serve as a time control. 2. In all 3 groups of animals, mesenteric and hindquarters vasoconstriction (beginning approximately 30 and 120 min, respectively, after water was removed) occurred much earlier than changes in blood pressure, since increases in blood pressure were significant only after 5-6 h of water deprivation; renal perfusion was largely unchanged. The observation of a differential onset of haemodynamic changes (i.e. mesenteric > hindquarters >> renal) extends our previous findings, in which measurements were made only at the end of a 14 h period of water-deprivation. 3. When given after 6 h of water deprivation, losartan and EXP 3174 produced directionally similar, but temporally disparate, haemodynamic effects. EXP 3174 caused a depressor response associated with marked renal, mesenteric and hindquarters vasodilatations which were well maintained over 2 h. Losartan evoked similar changes to EXP 3174 in the first 5 min, but in contrast to EXP 3174, blood pressure showed some recovery and all 3 vascular conductance values returned to baseline (i.e. pre-drug)levels over the following 10-20 min. Thereafter, hypotension and renal, mesenteric and hindquarters vasodilatation again occurred, and these changes were maintained for the rest of the 2 h. However,compared with losartan, EXP 3174 caused significantly greater mesenteric and hindquarters vasodilatation,even at times when both compounds lowered blood pressure to the same extent.4. The biphasic cardiovascular response caused by losartan is consistent with the conversion of the parent compound to EXP 3174. Whether or not the enhanced vasodilator effect of EXP 3174 over losartan is related to pharmacodynamic differences (i.e., noncompetitive versus competitive antagonism,respectively), and/or to differences in the amount of EXP 3174 generated from losartan is not known at present.

Angiotensin I↗
PubMed1993

Differential effects of captopril on regional haemodynamic responses to angiotensin I and bradykinin in conscious rats.

1. Conscious, Long Evans rats were chronically instrumented with pulsed Doppler flow probes and intravascular catheters to allow regional haemodynamic (coeliac, mesenteric and hindquarters vascular beds) responses to i.v. bradykinin to be assessed in the absence and presence of captopril and of ganglion blockade (with mecamylamine). 2. Bradykinin (3 nmol kg-1, i.v. bolus) had no effect on mean arterial blood pressure, although it caused hyperaemic vasodilatation in the coeliac, mesenteric and hindquarters vascular beds. Following administration of captopril at a dose (28 nmol kg-1) which had no effect on responses to angiotensin I, the hypotensive and coeliac and mesenteric vasodilator responses to bradykinin were enhanced. However, there was a temporal dissociation between these events indicating that changes in cardiac output must have been contributing to the changes in mean arterial blood pressure. 3. Captopril at a higher dose (280 nmol kg-1) caused reversible inhibition of the pressor and coeliac and mesenteric vasoconstrictor effects of angiotensin I, but the inhibition of the mesenteric vascular responses was significantly less than that of the coeliac vascular responses. Under the same conditions, the mesenteric vasodilator effects of bradykinin were less enhanced than the coeliac vasodilator effects, consistent with greater inhibition of angiotensin-converting enzyme (i.e., kininase II) in the coeliac than in the mesenteric vascular bed. But, since the hypotensive action of bradykinin was markedly enhanced in these circumstances, the possibility existed that baroreflex responses influenced the haemodynamic effects of bradykinin. However, assessment of the haemodynamic changes following bradykinin administration(bolus or infusion) in the presence of ganglion blockade showed that only the hindquarters vasodilator response to bradykinin was enhanced, while the coeliac and mesenteric vasodilator responses were diminished. Thus, additional factors must have been influencing the latter responses.4. The results show that inhibition of angiotensin-converting enzyme (kininase II) can have differential effects on the regional haemodynamic responses to angiotensin I and bradykinin. The results provide a striking illustration of our previous assertion that the measurement of arterial blood pressure alone cannot provide sufficient information to allow interpretation either of the effects of vasoactive substances,or of the influence of drugs thereupon.

Angiotensin I↗
PubMed1993

Effects of chronic treatment with nitric oxide synthase inhibitors on regional haemodynamic responses to vasodilators in conscious Brattleboro rats.

1. The effects of acute inhibition of nitric oxide (NO) synthase on cardiovascular responses to vasodilator challenges have already been described. We now report the responses to vasodilators during and after chronic NO synthase inhibition. 2. In conscious Brattleboro rats, the regional haemodynamic effects of 3 min infusions of acetylcholine (4 micrograms min-1), sodium nitroprusside (15 micrograms min-1) or adrenaline (0.2 micrograms min-1) were assessed (from areas under or over curves (AUC, AOC)) under control conditions, 6 and 72 h after the addition of the NO synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA) to the drinking water (1 mg ml-1), and 6, 24 and 48 h after the withdrawal of L-NMMA. In a separate group of Brattleboro rats, responses to acetylcholine, sodium nitroprusside and adrenaline were assessed before and 6 h after the onset of oral ingestion of the more potent nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.05 mg ml-1). 3. Acetylcholine caused renal vasodilation (87 +/- 11 units) and mesenteric vasoconstriction (-31 +/- 5 units), sodium nitroprusside caused vasodilatation in renal (96 +/- 12 units), mesenteric (222 +/- 13 units) and hindquarters (49 +/- 15 units) vascular beds, whereas adrenaline caused hindquarters vasodilatation (92 +/- 8 units). Seventy two h after the onset of oral ingestion of L-NMMA, acetylcholine had a decreased renal vasodilator (59 +/- 9 units) effect, sodium nitroprusside had an increased renal vasodilator (142 +/- 23 units) action, while adrenaline had a decreased hindquarters vasodilator (55 +/- 6 units) influence. Twenty four h after withdrawal of L-NMMA, the renal vasodilator effect of acetylcholine was greater than the control response (106 +/- 14 units), but the regional haemodynamic effects of sodium nitroprusside and adrenaline were not different from those under control conditions. Hence, the increased renal vasodilator response to acetylcholine was probably due to changes in muscarinic receptor-mediated mechanisms rather than to any increase in guanylyl cyclase or its sensitivity to NO.

Acetylcholine↗
PubMed1993

Regional haemodynamic effects of angiotensin II (3-8) in conscious rats.

1. It has been reported that angiotensin II (AII) (3-8) causes endothelium-dependent renal cortical vasodilatation, in anaesthetized rats, through interaction with a novel receptor that shows no affinity for the AT1-receptor antagonist, losartan. Therefore in order to get a fuller profile of the regional haemodynamic effects of AII (3-8) in conscious rats we assessed its renal, mesenteric and hindquarters vascular effects, and compared them to the responses elicited by AII and AIII. 2. AII and AIII (1.25, 12.5 and 125 pmol kg-1) caused dose-dependent pressor and renal and mesenteric vasoconstrictor effects. At doses up to 125 pmol kg-1, AII (3-8) was without any cardiovascular effects, but with doses of 1.25 and 12.5 nmol kg-1 there were dose-dependent increases in mean arterial blood pressure and reductions in renal and mesenteric flows and vascular conductances. The responses to AII (3-8) (12.5 nmol kg-1) were abolished by losartan (20 mumol kg-1). 3. Since it has been found that pretreatment with L-arginine can reveal a vasodilator effect of AII (3-8) on rabbit pial arterioles, we assessed responses to AII (3-8) (12.5 nmol kg-1) before and 5 min after onset of a primed infusion of L-arginine (1.4 mmol kg-1 bolus, 1.4 mmol kg-1 h-1 infusion). Responses to AII (3-8) were unchanged by L-arginine. 4. The results are consistent with AII (3-8) being a less effective agonist than All (or AIII) at the AT1-receptor, but provide no evidence for AII (3-8) interacting with a novel receptor that shows no affinity for losartan.

Amino Acid Sequence↗
PubMed1993

Regional and cardiac haemodynamic effects of NG, NG,dimethyl-L-arginine and their reversibility by vasodilators in conscious rats.

1. A series of experiments was carried out on 3 separate groups of male Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, to compare the effects of NG,NG, dimethyl-L-arginine (ADMA) and NG-monomethyl-L-arginine (L-NMMA), and their reversibility by the nitric oxide donors, S-nitroso-N-acetyl-penicillamine (SNAP), S-nitroso-glutathione (SNOG), sodium nitroprusside (SNP), and the vasodilator, hydralazine. 2. As previously reported for L-NMMA, ADMA (1-100 mg kg-1) caused dose-dependent pressor and bradycardic effects, accompanied by renal, mesenteric and hindquarters vasoconstrictions. The magnitude and duration of these effects were similar for ADMA and L-NMMA, consistent with their being equipotent inhibitors of nitric oxide synthase. 3. Infusion of SNAP or SNOG (300 micrograms kg-1 h-1) after injection of ADMA or L-NMMA (100 mg kg-1) reversed the pressor but did not abolish the vasoconstrictor, effects of ADMA or L-NMMA. However, a higher dose of SNAP (3 mg kg-1 h-1) caused complete reversal of the pressor and mesenteric haemodynamic effects of ADMA (100 mg kg-1), although its renal and hindquarters vasoconstrictor effects were not abolished. 4. Infusion of SNP (300 micrograms kg-1 h-1) after administration of L-NMMA (100 mg kg-1), caused complete reversal of its pressor and mesenteric and hindquarters haemodynamic effects, and reduced substantially its renal vasoconstrictor action; hydralazine (7.5 mg kg-1 h-1) was almost as effective as SNP in reversing all these variables. 5. In animals chronically instrumented for the measurement of cardiac haemodynamics, ADMA(100 mg kg-1) caused a pressor effect accompanied by a rise in central venous pressure, and reductions in heart rate, cardiac index, stroke index, peak aortic flow, maximum rate of rise of aortic flow and total peripheral conductance. The reversal of the pressor effect of ADMA by SNAP (300 microg kg-1 h-1) was accompanied by a reduction of central venous pressure below resting levels and a further diminution of stroke index; all other variables showed an increase, but they still remained below resting levels (with the exception of heart rate).6. Thus, following inhibition of NO synthesis, pharmacological intervention with NO donors, or other vasodilators, may cause normalisation of the mean arterial pressure without necessarily returning all associated cardiovascular variables to normal.

Animals↗
PubMed1993

Regional haemodynamic responses to intravenous and intraarterial endothelin-1 and big endothelin-1 in conscious rats.

1. In the same chronically-instrumented conscious Long Evans rats, we assessed regional haemodynamic responses to i.v. and i.a. injections of endothelin-1 (ET-1) and big endothelin-1 at doses of 0.05 (n = 4) and 0.5 nmol kg-1 (n = 7). 2. For ET-1, the cardiovascular effects (initial hypotension and tachycardia with transient hindquarters vasodilation, followed by hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions) of i.v. and i.a. injections were not different. 3. Similarly, for big ET-1, the cardiovascular effects (hypertension, bradycardia and renal, mesenteric, and hindquarters vasoconstrictions) of i.v. and i.a. injections were not different. 4. At a dose of 0.5 nmol kg-1, i.v. or i.a., the pressor effects of ET-1 and big ET-1 were not different(area under curve [AUCO-30m.), ET-1 i.v. = 786 +/- 115 mmHg min; ET-1 i.a. = 880 +/- 165 mmHg min;big ET-1 i.v. = 878 +/- 93 mmHg min; big ET-1 i.a. = 833 +/- 103 mmHg min); but ET-1 caused greater renal, and lesser hindquarters, vasoconstrictions than big ET-1 (renal ET-1 i.v., AOC = 1550 +/- 211%min; ET-1 i.a., AOC = 1746 +/- 139% min; big ET-1 i.v., AOC = 1097 +/- 128% min; big ET-1 i.a.,AOC = 1041 +/- 119% min; hindquarters, ET-1 i.v., AOC = 758 +/- 176% min; ET-1 i.a. AOC =787 +/- 184% min; big ET-1 i.v., AOC = 1270 +/- 88% min; big ET-1 i.a., AOC = 1173 +/- 77% min), while the mesenteric vasoconstrictor effects of both peptides were not significantly different (ET-1 i.v.AOC = 1419 +/- 132% min; ET-l i.a., AOC = 1526 +/- 172% min; big ET-1 i.v., AOC = 1099 +/- 166%min; big ET-1 i.a., AOC = 1155 +/- 120% min).5. Under the conditions of our experiments, pulmonary clearance of ET-1, or pulmonary activation of big ET-1, was not apparent from the haemodynamic responses to i.v. and i.a. administration of the peptides. The results are consistent with previous findings indicating that local, rather than systemic,conversion of exogenous big ET-1 to ET-1 is responsible for its regional haemodynamic actions.

Animals↗
PubMed1993

Central administration of PD 123319 or EXP-3174 inhibits effects of angiotensin II.

Cardiovascular responses to intracerebroventricular angiotensin II (ANG II) were measured in conscious rats, chronically instrumented for the measurement of regional hemodynamics, over 4 consecutive days in the absence and presence of either the AT2 receptor antagonist, PD 123319 (experiment 1), or the AT1 receptor antagonist, EXP-3174 (experiment 2). Intracerebroventricular ANG II had pressor and bradycardic effects, which were associated with marked mesenteric and hindquarters vasoconstriction, and a small transient renal vasoconstriction. Both PD 123319 and EXP-3174, given intracerebroventricularly, abolished the cardiovascular response to intracerebroventricular ANG II, although the profiles of activity of the compounds were different. PD 123319 caused a slowly developing, but remarkably prolonged (1-2 days) inhibition of the effects of ANG II, whereas EXP-3174 caused an immediate inhibition of the effects of ANG II, although responses to ANG II had returned to control levels by the following day. These data suggest that the hemodynamic effects of ANG II may involve concurrent, and interdependent, activation of AT1 and AT2 receptors or that PD 123319 undergoes a unique biotransformation in the brain to some product(s) with AT1 receptor antagonist activity.

Angiotensin II↗
PubMed1993

Differential blockade of central effects of angiotensin II by AT2-receptor antagonists.

In conscious, chronically instrumented, male Long-Evans rats, we showed previously that central administration (intracerebroventricular) of the AT1-receptor antagonist EXP-3174 (1 microgram) caused a rapid-onset marked, but transient, blockade of the regional hemodynamic responses to intracerebroventricular angiotensin II (ANG II). In contrast, the AT2-receptor antagonist PD-123319 (80 micrograms) caused a slow-onset, but marked and persistent, antagonism of the effects of intracerebroventricular ANG II. In the present study we attempted to mimic the actions of PD-123319 by giving a supramaximal dose of EXP-3174 (10 micrograms), and we also assessed the effects of PD-123177 (80 micrograms), an AT2-receptor antagonist that differs from PD-123319 only by a dimethyl group. The higher dose of EXP-3174 did not exert prolonged antagonistic effects against responses to intracerebroventricular ANG II, and PD-123177 was without inhibitory effects in this model. The results indicate important functional differences between putative AT2-receptor antagonists, when assessed in vivo, that are not apparent from binding studies.

Angiotensin II↗
PubMed1993

Regional haemodynamics in Brattleboro rats during chronic ingestion of NG-nitro-L-arginine methyl ester.

The aim of this study was to assess regional haemodynamic changes in conscious Brattleboro rats during chronic ingestion of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME). Animals were instrumented with renal, mesenteric and hindquarters pulsed Doppler flow probes and an intra-arterial catheter, and haemodynamic measurements were made before, during and after 14 days' exposure to L-NAME (0.01 mg ml-1 in the drinking water). Within 6 h after addition of L-NAME to the drinking water, mean arterial blood pressure was increased (maximum, 33 +/- 6 mm Hg), and remained so until L-NAME was withdrawn, whereupon blood pressure returned to normal levels within 24 h. The hypertension was accompanied by a transient reduction in mesenteric blood flow, and a more persistent reduction in hindquarters blood flow. Mesenteric and, particularly, hindquarters vascular conductance showed a sustained reduction. However, during ingestion of L-NAME, renal blood flow was not diminished and, over the final 4 days of exposure to L-NAME there was no significant renal vasoconstriction. All regional haemodynamic effects of L-NAME were lost within 24 h of its withdrawal. Hence, as with shorter periods of exposure to the less potent NO synthase inhibitor, NG-monomethyl-L-arginine, the hypertension caused by L-NAME is dependent on its continued administration, and is associated with a particularly marked hindquarters vasoconstriction.

Animals↗
PubMed1992

Nitric oxide synthase inhibitors cause sustained, but reversible, hypertension and hindquarters vasoconstriction in Brattleboro rats.

Homozygous male Brattleboro rats were given a solution of NG-monomethyl-L-arginine (L-NMMA; 1 mg ml-1) to drink for a period of 7 days. There was a persistent elevation of mean arterial blood pressure, accompanied by a significant hindquarters vasoconstriction. Within 9 h of withdrawal of L-NMMA all variables were not different from pre-L-NMMA values. Brattleboro rats (n = 3) which had been drinking NG-nitro-L-arginine methyl ester (L-NAME) solution (0.05 mg ml-1) for 5-6 months showed an increased blood pressure which reversed to normal within 48 h after withdrawing the L-NAME. Thus, inhibition of nitric oxide synthesis leads to long-lasting, but reversible, hypertension.

Amino Acid Oxidoreductases↗
PubMed1992

Amlodipine combined with beta blockade for chronic angina: results of a multicenter, placebo-controlled, randomized double-blind study.

Amlodipine, a potent long-acting dihydropyridine calcium antagonist, was compared with placebo in a parallel, randomized, double-blind study in 134 patients with chronic stable angina pectoris maintained on beta-adrenergic blocking agents. After a single-blind, two-week placebo period, patients were randomized to receive either amlodipine (2.5, 5, and 10 mg) or placebo once daily for four weeks. The effects of amlodipine on maximal exercise time, work, time to angina onset, and subjective indices including angina frequency, nitroglycerin tablet consumption, and patient and investigator ratings were assessed. Each dose of amlodipine produced increases in exercise time and calculated total work accomplished compared to baseline. Improvements at 5 and 10 mg were significantly greater than placebo which produced no significant change (p less than 0.05). Qualitative improvements in the severity of angina were produced by amlodipine at 5 and 10 mg daily assessed by patient-rating questionnaires (p less than 0.05). Reductions in angina frequency attacks per week and weekly nitroglycerin tablet consumption occurred but were not statistically significant when compared with placebo. Adverse effects observed during amlodipine treatment prompted discontinuation of treatment in only 2 out of 100 patients. Three patients discontinued treatment for reported lack of efficacy. No laboratory abnormalities prompted treatment discontinuation and minor side effects of dizziness, nausea, headache, and fatigue were observed infrequently. The results of this controlled, large-scale multicenter trial suggest that amlodipine significantly increased exercise capacity and was well tolerated when added to the antianginal regimen of patients remaining symptomatic while receiving beta-blocking agents.

Adolescent↗
PubMed1992

Marital status and infant health outcomes.

Out-of-wedlock status has long been recognized as a demographic risk factor associated with infant mortality and low birthweight. However, the relationship between marital status and birth outcomes varies by maternal race and age. The negative impact of unmarried status is greatest for white women aged 20 and over. High infant mortality rates for married teen mothers challenge the assumption that marriage necessarily provides a protective environment for childbearing. Maternal and child health research and policy have been hindered by a deviance model of out-of-wedlock fertility, which is both biased and outdated. Inconsistencies in the effect of marital status indicate variations in both economic and social resources. Purely behavioral explanations for escalated risks to unmarried mothers are not justified by research findings. Alternative interpretations suggest the need for greater societal involvement in maternal health care created in part by changes in family structure.

Adolescent↗
PubMed1992

Regional haemodynamic effects of noradrenaline injected into the hypothalamic paraventricular nuclei of conscious, unrestrained rats: possible mechanisms of action.

The cardiovascular effects of noradrenaline bilaterally injected into the hypothalamic paraventricular nuclei were investigated in conscious, unrestrained Long-Evans rats and homozygous, vasopressin-deficient Brattleboro rats, chronically instrumented with pulsed Doppler probes for measurement of regional haemodynamics. In Long-Evans rats, incremental doses of noradrenaline (0.01-10 nmol) caused dose-related increases in blood pressure and a substantial, dose-related, superior mesenteric vasoconstriction. These changes were accompanied by bradycardia and reductions in renal and hind-quarter vascular conductances. In Brattleboro rats, noradrenaline (10 nmol) had no effect on blood pressure, heart rate, or renal or superior mesenteric vascular conductances. However, there was a slight vasodilatation in the vascular bed of the hindquarters. In Long-Evans rats, intravenous pretreatment with phentolamine had no effect on the bradycardia but partly inhibited the pressor response to noradrenaline injected into the paraventricular nuclei. These effects were associated with a smaller superior mesenteric vasoconstriction and an abolition of the vasoconstriction in the hindquarters. Combined intravenous pretreatment with phentolamine and propranolol had no effect on the heart rate or pressor responses to noradrenaline injected into the paraventricular nuclei, but reduced the superior mesenteric vasoconstriction, potentiated the vasoconstriction in the hindquarters and eliminated the renal vasoconstriction. These results suggest that, in untreated Long-Evans rats, alpha-adrenoceptor-mediated constriction in the mesenteric vascular bed and beta-adrenoceptor-mediated dilatation in the vascular bed of the hindquarters have important influences on the pressor response to noradrenaline injected into the paraventricular nuclei. In the presence of the vasopressin V1-receptor antagonist, d(CH2)5[Tyr(Et)]DAVP, the pressor and heart rate responses to noradrenaline injected into the paraventricular nuclei were abolished, as were the vasoconstrictions in the renal, superior mesenteric and hindquarter vascular beds. Together these results suggest an interaction between the sympathoadrenal system and vasopressin-mediated mechanisms in the cardiovascular responses to noradrenaline injected bilaterally into the paraventricular nuclei of conscious, untreated rats.

Animals↗
PubMed1992

The influence of atropine and atenolol on the cardiac haemodynamic effects of NG-nitro-L-arginine methyl ester in conscious, Long Evans rats.

1. In the present study, the extent to which baroreflexes contribute to the cardiac effects of NG-nitro-L-arginine methyl ester (L-NAME) was assessed in conscious, Long Evans rats chronically instrumented with thoracic electromagnetic flow probes for the measurement of cardiac haemodynamics. 2. L-NAME (10 mg kg-1, i.v.) was administered in the absence (n = 6) and in the presence (n = 7) of atropine (1 mg kg-1) and atenolol (1 mg kg-1). 3. L-NAME caused a marked increase in mean arterial pressure and marked reductions in total peripheral conductance, cardiac output, heart rate, stroke volume, peak thoracic flow and the maximum rate of rise of aortic flow. 4. Administration of atropine, after the maximal bradycardic effect of L-NAME was established, restored the heart rate to resting levels. Concurrently, there was a reduction in stroke volume, such that cardiac output, although transiently elevated, did not show a sustained increase. No other variables were significantly affected by atropine. Additional administration of atenolol had no effect other than to cause a slight bradycardia, such that in the presence of atropine and atenolol, heart rate was not different from that in animals receiving atropine and atenolol before L-NAME. 5. In the presence of atropine and atenolol, L-NAME had similar pressor, vasoconstrictor and cardiac haemodynamic effects to those in untreated animals, although the bradycardia was significantly attenuated. However, there was still a significant reduction in heart rate following L-NAME in the presence of atropine and atenolol.6. These results indicate that the major component of the bradycardia following L-NAME is indirect and mediated through an increase in vagal efferent activity. However, the substantial reduction in cardiac function caused by L-NAME is not dependent on the autonomic control of the heart but rather, may depend on the increase in afterload and/or a direct effect of L-NAME on the heart and/or its vasculature.

Animals↗
PubMed1992

Involvement of beta 2-adrenoceptors in the regional haemodynamic responses to bradykinin in conscious rats.

1. Bradykinin can release neuronal calcitonin gene-related peptide (CGRP) and adrenal medullary catecholamines, both of which could contribute to its cardiovascular effects in vivo. Therefore, in the main experiment, regional haemodynamic responses to bolus injections of bradykinin (3 nmol kg-1, i.v.) were assessed in the same chronically-instrumented, conscious, Long Evans rats in the absence and in the presence of human alpha-CGRP [8-37] or ICI 118551, antagonists of CGRP1-receptors and beta 2-adrenoceptors, respectively. The selected doses of these antagonists caused specific inhibition of responses mediated by exogenous human alpha-CGRP and beta 2-adrenoceptor agonists, respectively. 2. Bradykinin administered alone as an i.v. bolus had a slight pressor effect accompanied by a marked tachycardia. There were early (at about 30 s) increases in flow and conductance in the mesenteric vascular bed, and delayed (at about 90 s), but qualitatively similar, changes in the hindquarters vascular bed. There were only slight increases in flow and conductance in the renal vascular bed. 3. Human alpha-CGRP [8-37] had no statistically significant effects on the responses to bolus doses of bradykinin. However, in the presence of ICI 118551, the pressor effect of bradykinin was significantly enhanced while its tachycardic effect was significantly suppressed. The hindquarters vasodilator effect of bradykinin was converted to a vasoconstriction and there was a slight renal vasoconstriction, but the mesenteric vasodilator effect of bradykinin was unchanged by ICI 118551. 4. In subsidiary experiments, in other animals, it was found that infusion of bradykinin (36 nmol kg-1 min-1) elicited a pattern of haemodynamic responses similar to that seen with bolus injections and, as in the latter case, the hindquarters hyperaemic vasodilation was inhibited by ICI 118551. In the presence of mecamylamine (at a dose sufficient to block reflex heart rate responses to rises or falls in arterial blood pressure) bolus injection or infusion of bradykinin still elicited increases in renal, mesenteric and hindquarters blood flow. However, in additional experiments in adrenal demedullated rats (n = 4) the hindquarters hyperaemic effect of bradykinin was absent, although the mesenteric hyperaemic effect remained. 5. The results indicate that the increase in hindquarters blood flow following administration of bradykinin in vivo is largely due to activation of beta 2-adrenoceptors by catecholamines released subsequent to direct stimulation of the adrenal medulla by the peptide. However, the bradykinin-induced increase in mesenteric blood flow does not depend on this mechanism.

Adrenal Medulla↗