bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARATIVE EFFECTS OF DOPAMINE AND DOBUTAMINE ON THE PULMONARY HAEMODYNAMIC RESPONSE TO HYPOXIA IN DOGS VENTILATED WITH A HYPOXIC GAS MIXTURE
Authors: Tanaka Hiroyuki , Tajimi Kimitaka , Kasai Takeshi , Kobayashi Kunio
Published: June 2007

1. The effects of dopamine and dobutamine on the pulmonary haemodynamic response to hypoxia were studied in nine anaesthetized dogs under hypoxaemia induced by ventilation with hypoxic gas mixture.

2. From the present study, only dopamine infusion reduced arterial oxygenation during hypoxic hypoxaemia, whereas catecholamine maintained it at the same level during normoxaemia.

3. A redistribution of perfusion to the pulmonary vasculature may be related to a reduction of arterial oxygenation with dopamine infusion during hypoxic hypoxaemia.

4. It is presumed that an increase in pulmonary blood flow would emphasize an inhibition of hypoxic pressor response in the pulmonary vasculature, which may not be a direct effect of dopamine.
CIRCULATING ANGIOTENSIN II LEVELS UNDER REPEATED ADMINISTRATION OF LISINOPRIL IN NORMAL SUBJECTS
Authors: Kawamura Minoru , Imanashi Masahito , Matsushima Yohkazu , Ito Keiichi , Hiramori Katsuhiko
Published: June 2007

1. To examine the effect of chronic administration of angiotensin I‐converting enzyme (ACE) inhibitor on circulating angiotensin II (All) concentration, 20 mg of lisinopril was administered once daily for 7 consecutive days to eight healthy volunteers.

2. Plasma ACE activity was inhibited to less than approximately 30% of the pretreatment level during the repeated administration.

3. Mean arterial pressure (MAP) was slightly but significantly reduced during the administration period. Plasma All concentration measured by an established method using high performance liquid chromatography combined with a radioImmunoassay, however, was maintained at approximately the pretreatment level when it was measured at 24 h intervals after each administration of lisinopril.

4. With the gradual recovery of ACE activity following discontinuation of administration, the plasma All concentration correlated with AI concentration (r= 0.46), and also with the product of AI and ACE activity (AI X ACE; r= 0.80), corresponding to the formula obtained from the kinetics of ACE activity. No correlation was observed between MAP and All levels throughout the study period.

5. We conclude that in normal subjects repeatedly administered with ACE inhibitor, the All level in the circulation is still determined by an elevated level of AI and any remaining ACE activity, thus maintaining All at pretreatment levels. We confirmed that it is not necessary to achieve a decrease in plasma All concentration through the chronic administration of ACE inhibitor in order to effectively lower blood pressure.
EFFECTS OF CHRONIC ADMINISTRATION OF ANTIHYPERTENSIVE DRUGS ON VASODILATION MEDIATED BY CALCITONIN GENE‐RELATED PEPTIDE‐CONTAINING VASODILATOR NERVES IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kawasaki Hiromu
Published: June 2007

1. The effects of chronic administration of antihypertensive drugs on the vasodilator response mediated by calcitonin gene‐related peptide (CGRP)‐containing nerves were investigated in spontaneously hypertensive rats (SHR).

2. A 7 week period of antihypertensive treatment with captopril, nicardipine or propranolol during the developmental phase (8–15 weeks of age) significantly lowered the mean blood pressure of SHR when compared with non‐treated SHR.

3. The mesenteric vascular beds isolated from SHR, which were chronically administered with captopril, propranolol or nicardipine, were perfused with Krebs’ solution containing 7/μmol/L methoxamine to produce active tone and 5 μmol/L guanethidine to block adrenergic neurotransmission.

4. In the mesenteric vascular bed with active tone, perivascular nerve stimulation (PNS; 0.5–8 Hz) caused a frequency‐dependent vasodilator response that was abolished by 100 nmol/L tetrodotoxin (neurotoxin) or 1 μmol/L CGRP (8–37), a CGRP receptor antagonist.

5. CGRP‐containing nerve‐mediated vasodilator responses were significantly greater in cap‐topril‐treated SHR and significantly smaller in nicardipine‐treated SHR than in non‐treated SHR. There was no difference between the response between propranolol‐treated SHR and non‐treated SHR.

6. These results suggest that chronic treatment with captopril reverses the reduced neurogenic vasodilation mediated by CGRP‐containing nerves in SHR.
EFFECTS OF ARGININE VASOPRESSIN, ANGIOTENSIN II AND ENDOTHELIN‐1 ON THE RELEASE OF BRAIN NATRIURETIC PEPTIDE IN VIVO AND IN VITRO
Authors: Horio Takeshi , Kohno Masakazu , Takeda Tadanao
Published: June 2007

1. The stimulatory effects of the vasoactive peptides arginine vasopressin (AVP), angiotensin II (AII) and endothelin‐1 (ET‐1) on the release of brain natriuretic peptide (BNP) were investigated in anaesthetized rats and in cultured rat atrial and ventricular cardiocytes.

2. A bolus injection of AVP induced a dose‐dependent increase in plasma immunoreactive (ir)‐BNP concentration in rats. AII induced a rapid and transient elevation in the ir‐BNP level, while the increase produced by ET‐1 was long‐lasting. The elevation of the plasma ir‐BNP concentration after stimulation by these three vasoconstrictors appeared to be paralleled by the elevation in mean blood pressure.

3. In the in vitro study, the rat atrial and ventricular cardiocytes both secreted ir‐BNP into the medium in a time‐dependent manner. ET‐1 clearly stimulated the secretion of ir‐BNP in both atrial and ventricular cardiocytes. In contrast, AVP and AII had no stimulatory effect in vitro.

4. Reverse‐phase high performance liquid chromatography of the rat plasma and culture medium revealed a single major ir‐BNP component that corresponded to synthetic rat BNP‐45.

5. These observations indicate that AVP, AII and ET‐1 stimulate the release of ir‐BNP (probably rat BNP‐45) through a change in blood pressure. In addition, ET‐1 may also induce ir‐BNP release through direct stimulation. As a cardiac hormone secreted from ventricles as well as atria, rat BNP may play a role in the regulation of blood pressure against the pressor effects of AVP, AII and ET–1.
DIETARY Ng‐NITR0‐l‐ARGININE INDUCES SUSTAINED HYPERTENSION IN NORMOTENSIVE WISTAR‐KYOTO RATS
Authors: Ikeda K. , Jr O. G. Gutierrez , Yamori Y.
Published: June 2007

1. Prolonged oral administration of NG‐nitro‐l‐arginine (l‐NNA) for a period of 5 weeks in 8 week old male normotensive Wistar‐Kyoto (WKY) rats n= 10), induced hypertension in all animals. Hypertension was characterized by a sharp initial increase in both systolic blood pressure (SBP) and mean blood pressure (MBP) until the third day (from 126 ± 3 mmHg to 160 ± 6 mmHg and from 95 ± 3 mmHg to 133 ± 6 mmHg, respectively). This was followed by a gradual and steady increase until the fourth week (163 ± 4, 171 ± 3 and 189 ± 8 mmHg for SBP in weeks 1, 2 and 4, respectively; and 135 ± 4, 143 ± 3and 157 ±5 mmHg for MBP in weeks 1, 2 and 4, respectively).

2. Intravenously L‐arginine‐HCl (500 mg/kg) administered on the last day of the 5th week abolished the effect of dietary l‐NNA on the arterial blood pressure.

3. Dietary l‐NNA‐induced hypertension in WKY rats is easily obtainable and free of any surgical operation, and can be utilized as a new experimental model to further understand the importance of endothelium‐dependent relaxing factor/nitric oxide in blood pressure regulation and to clarify the pathological significance in intact animals where endothelium‐dependent relaxing factor/nitric oxide is functionally involved.
ENHANCEMENT BY ENDOTHELIN‐1 OF THE RELEASE OF CATECHOLAMINES FROM THE CANINE ADRENAL GLAND IN RESPONSE TO SPLANCHNIC NERVE STIMULATION
Authors: Takeuchi Akihiko , Kimura Tomohiko , Satoh Susumu
Published: June 2007

1. The effect of endothelin‐1 on the release of adrenal catecholamines was examined in anaesthetized dogs.

2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz was applied before and after the intravenous injection of endothelin‐1.

3. Endothelin‐1 (0.1 and 0.3 μg/kg) significantly enhanced the release of adrenal catecholamines induced by 3 Hz SNS, but did not affect basal release and the release of adrenal catecholamines induced by 1 Hz SNS.

4. Endothelin‐1 produced a slight and short‐lasting fall in arterial blood pressure and decreases in adrenal and renal blood flow rates.

5. These results indicate that endothelin‐1 enhances the release of adrenal catecholamines from the canine adrenal gland in response to relatively high frequency SNS.
THE CLINICAL PHARMACOLOGY OF ACE INHIBITORS: EVIDENCE FOR CLINICALLY RELEVANT DIFFERENCES?
Authors: Lees Kennedy R. , Squire Iain B. , Reid John L.
Published: June 2007

1. Potential differences among ACE inhibitors include pharmacokinetic and pharmacodynamic factors. The presence of a sulfhydryl group conferring antioxidant properties, the administration as a pro‐drug to delay the onset and prolong the duration of haemodynamic effects, and the route of elimination are examples of possible differences.

2. Adverse effects of ACE inhibitors may be mediated by effects on bradykinin metabolism at tissue sites, which may be separable from haemodynamic responses mediated largely by angiotensin II withdrawal.

3. Clinically important differences between ACE inhibitors in their adverse event profile have yet to be proven. Evidence is emerging that plasma ACE inhibition and haemodynamic responses are separable, and this may indicate the potential for other organ‐specific effects to differ among ACE inhibitors.

4. At present, however, the greatest distinguishing features for one compound vs another are the time to onset and the duration of action, which determine the frequency of administration.
CEREBROVASCULAR PROTECTION BY SEQUENTIAL BILATERAL CAROTID ARTERY LIGATION IN AGED SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Horie R. , Mano M. , Omura K.
Published: June 2007

1. Sequential bilateral carotid artery ligation (BCL) separated by a 1 week interval was performed on 5 month spontaneously hypertensive rats (SHR) (i.e. SHRSR‐B1/Izm) and the developmental course of hypertension and cerebrovascular lesions in advanced age were analysed as compared with those in age‐matched sham‐operated controls.

2. Behavioural activity and behavioural reaction to light were also investigated in the above‐mentioned SHR, young and adult stroke‐prone SHR (i.e. SHRSP‐A3/Izm), SHR (i.e. B1/Izm) and Wistar‐Kyoto rats (i.e. WKY/Izm).

3. All of the control SHR developed severe hypertension resulting in cerebral stroke with focal oedema due to cerebral haemorrhage and infarction as a result of arterionecrosis 18 months after birth.

4. SHR usually die within a few days of BCL. In the present study, however, they successfully survived without cerebrovascular damage for a long time, although they developed a similar severe hypertension in a significantly shorter period of time (P < 0.05) and showed behavioural abnormalities that were probably due to severe cerebral ischaemia.

5. These experimental results suggest an ischaemic tolerance phenomenon in a hypertensive model that was exposed to mild ischaemic stress by unilateral carotid artery ligation (UCL) before the subsequent induction of severe ischaemia by BCL. The results also suggest that an aggravation of hypertensive cerebrovascular changes due to long‐lasting ischaemia after BCL was prevented through a possible cumulative effect of ischaemic stress.
CIRCULATING LEVELS OF ACTIVE, TOTAL AND INACTIVE RENIN (PRORENIN), ANGIOTENSIN I AND ANGIOTENSINOGEN IN CARBON TETRACHLORIDE‐TREATED RATS
Authors: Cruz Cristino , Ibarra‐Rubio Maria Elena , Pedraza‐Chaverrí José
Published: June 2007

1. Plasma renin activity (PRA), plasma angiotensin I concentration (ANG I), plasma angiotensinogen concentration (PAC) and the plasma levels of active, total and inactive renin (prorenin) were measured in rats with carbon tetrachloride (CCl4)‐induced acute renal failure. Rats were treated with a single oral dose of CCl4 (2.5 mL/kg) and killed 1, 2, 3 and 7 days later.

2. On days 1–3 PRA, ANG I and PAC decreased and increased on day 7. Active renin fell on days 2 and 3, total renin (trypsin treatment) augmented on day 1 and diminished on day 3, prorenin and per cent prorenin increased on days 1 and 2. Angiotensin I concentration paralleled PRA and PAC. The CCl4‐induced decrease in PRA was secondary to the fall in active renin and in PAC. Total renin augmented as a consequence of the elevation of prorenin. Renal function, evaluated by serum urea, serum creatinine and creatinine clearance, decreased on days 1 and 2 when PRA was low and plasma prorenin was high.

3. These data do not support the involvement of the circulating active renin‐angiotensin system (RAS) in the pathophysiology of acute renal failure induced by CCl4, however, increased prorenin levels were associated with the decrease in renal function.
EFFECTS OF ADENOSINE AND ITS ANALOGUES ON ACTIN POLYMERIZATION IN HUMAN POLYMORPHONUCLEAR LEUCOCYTES
Authors: Tsuruta Satoru , Ito Setsuko , Mikawa Haruki
Published: June 2007

1. The effects of adenosine and its analogues on actin polymerization in human polymorphonuclear leucocytes (PMN) induced by three different chemotactic stimulants, platelet‐activating factor (PAF), N‐formyl‐methionyl‐leucyl‐phenylalanine (FMLP) and an activated fragment of C5 (C5a) were investigated.

2. Adenosine and its analogues inhibited the actin polymerization induced by these three agents in a concentration‐dependent manner and theophylline, a competitive antagonist at adenosine receptors, abolished these inhibitory effects.

3. The adenosine analogue 5′‐N‐ethylcarboxamideadenosine (NECA) was a more potent inhibitor of actin polymerization than either l‐N6‐phenylisopropyladenosine (PIA) or adenosine itself; the rank order of potency of these agonists was characteristic of adenosine A2 receptors.

4. Adenosine deaminase (ADA) abolished the inhibitory effect of adenosine and augmented PAF‐induced actin polymerization.

5. It was concluded that, at physiological concentrations, adenosine inhibits actin polymerization in PMN via activation of PMN surface membrane adenosine A2 receptors and thus modulates chemotactic stimulus‐induced PMN motility.
MORPHINE AND MORPHICEPTIN INCREASE THE THRESHOLD FOR EPINEPHRINE‐INDUCED CARDIAC ARRHYTHMIAS IN THE RAT THROUGH BRAIN MU OPIOID RECEPTORS
Authors: Rabkin Simon W.
Published: June 2007

1. To determine whether morphine modulates the development of cardiac arrhythmias through mu opioid receptors by an action within the central nervous system (CNS). Catecholamine‐induced ventricular arrhythmias were produced, in the rat, by continuous infusion of epinephrine at incremental doses until the development of fatal arrhythmias, usually ventricular fibrillation.

2. Morphine, 0.1 mg/kg i.v., significantly suppressed (P < 0.05) the development of epinephrine‐induced arrhythmias compared with the control group. This was opposed by the mu opioid antagonist naloxone (1 or 2 mg/kg) in a dose‐dependent manner.

3. To determine whether these effects were operative in the brain, rats received an injection of either morphine 50 μg/kg or its diluent (control) into the lateral cerebral ventricle intracerebroventricularly (i.c.v.). Morphine significantly increased (P < 0.05) the threshold for the development of arrhythmias.

4. To further explore whether this effect was operative at the mu opioid receptor, a more specific mu opioid receptor agonist morphiceptin (50 mUg/kg) was administered i.c.v. and produced a significant increase (P < 0.05) in the threshold for cardiac arrhythmias compared with controls.

5. The action of morphine was further established to be operating through mu opioid receptors from experiments with the i.c.v. administration of naloxone (+) and naloxone (—) followed by morphine showing that the action of morphine in the brain was prevented by the opioid antagonist naloxone but not by its stereo‐isomer that is not a mu opioid receptor antagonist.

6. These data suggest a role for morphine to modulate cardiac arrhythmias, specifically to increase arrhythmia threshold, through an action within the CNS at mu opioid receptors.
EFFECTS OF CORTISOL ON BLOOD PRESSURE AND SALT PREFERENCE IN NORMAL HUMANS
Authors: Wong K. S. , Williamson P. M. , Brown M. A. , Zammit V. C. , Denton D. A. , Whitworth J. A.
Published: June 2007

1. Adrenocorticotrophic hormone (ACTH) and corticosteroids stimulate salt appetite in laboratory animals. The hypothesis tested was that cortisol administration increases salt preference in humans.

2. Sodium taste studies (detection and recognition thresholds, taste intensity and preference tests) were conducted before, during and after cortisol administration (200 mg/day for 5 days) in normal men on a free diet.

3. Cortisol significantly increased systolic blood pressure (SBP), 113 ± 3–130±4 mmHg, P < 0.05; diastolic blood pressure (DBP), 65±3–81±2 mmHg, P < 0.05; mean arterial pressure (MAP), 81± 2–97± 3 mmHg, P < 0.05; and bodyweight, 72.9±3.0–75.4±3.3 kg, P < 0.05.

4. Salt detection and recognition thresholds, taste intensity and preference for sodium chloride were unchanged following cortisol.
α‐AND β‐ADRENOCEPTOR AGONIST ACTIVITY IN THE VENOM OF THE AUSTRALIAN HUNTSMAN SPIDERS, DELENA CANCERIDES AND ISOPEDA MONTANA
Authors: Korszniak N. V. , Story D. F.
Published: June 2007

1. Crude venom gland extracts (VGE) were prepared from female Delena cancerides and Isopeda montana spiders. The VGE were tested in isolated rat atrial, caudal artery and pithed rat preparations for pharmacological activity.

2. In rat isolated atrial preparations, D. cancerides and I. montana VGE, each in a concentration of 2 glands/mL, produced increases in atrial rate which were abolished by propranolol (1 μmol/L) but not by ketanserin (0.1 μmol/L) or reserpine pretreatment (2.5 mg/kg s.c. 24 h prior to experimentation) indicating a direct action on atrial β‐adrenoceptors.

3. In rat caudal artery preparations each VGE produced an increase in perfusion pressure, which was taken as an index of vasoconstriction. Pressor responses to D. cancerides VGE (1 gland/mL) were abolished in the presence of prazosin (1 mol/L) but not by reserpine pretreatment, indicating an action of the VGE on vascular α1‐adrenoceptors. Neither prazosin nor reserpine pretreatment had any effect on pressor responses of rat caudal artery preparations to I. montana VGE. Ketanserin (6 nmol/L) produced a small reduction in the degree of vasoconstriction produced by the VGE. This demonstrates a lack of α1‐adrenoceptor agonist activity of the VGE.

4. Both VGE produced dose‐dependent increases in mean arterial pressure and heart rate in pithed rat preparations. The use of relatively selective receptor antagonists indicated that the increases in mean arterial pressure (MAP) produced by both VGE were mediated by an action on α2‐adrenoceptors.
A SIMPLE METHOD FOR ESTIMATING 24 H URINARY SODIUM AND POTASSIUM EXCRETION FROM SECOND MORNING VOIDING URINE SPECIMEN IN ADULTS
Authors: Kawasaki Terukazu , Itoh Kazue , Uezono Keiko , Sasaki Haruka
Published: June 2007

1. An assessment was made of the extent sodium (Na) and potassium (K) intake can be estimated from Na, K and creatinine (Cr) content of a second morning voiding urine (SMU) specimen collected within 4 h after the first voiding upon awakening but before breakfast in 159 clinically healthy, free‐living individuals (20–79 years). The SMU and the rest of 24 h urine specimens for a 3–5 day period were collected.

2. The following equations for estimating 24 h urinary Na (24HUNaV) and K (24HUKV) excretions were developed, and the accuracy and the reliability of these equations were evaluated. Estimated value of 24HUNaV (mEq/day) = 16.3 √XNa; estimated value of 24HUKV (mEq/day) = 7.2 √XK, where XNa (or XK) = SMUNa (or SMUK)/SMUCr X predicted 24 h urinary Cr excretion.

3. Highly statistically significant correlations were detected between the values estimated and measured for both Na (r= 0.728, P < 0.001, n= 159) and K (r= 0.780, P < 0.001, n= 159).

4. These equations were applied to Group 1 subjects, who collected the urine for a single day, and to Group 2, for 3 days. The correlation coefficients between the values estimated and measured for Na and K were 0.531 and 0.443 in Group 1, and 0.821 and 0.590 in Group 2, respectively. No statistically significant differences were observed.

5. The SMU specimens provide a satisfactory alternative to both 24HUNaV and 24HUKV in adults for extensive epidemiological surveys but also for clinical application.
DISCREPANCY BETWEEN RENIN mRNA AND PLASMA RENIN LEVEL IN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR‐TREATED RATS
Authors: Morishita Ryuichi , Higaki Jitsuo , Nagano Masahiro , Nakamura Fumiaki , Tomita Naruya , Zhao Yi , Mikami Hiroshi , Miyazaki Mizuo , Ogihara Toshio
Published: June 2007

1. To investigate the role of transcriptional and post‐transcriptional factors in increasing renin synthesis secondary to angiotensin‐converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors.

2. Spontaneously hypertensive rats were orally administered 10 mg/kg spirapril or vehicle daily for 3, 14 or 28 days.

3. Plasma renin activity in the spirapril‐treated group was significantly elevated compared with that in the vehicle group at any time (P<0.01). However, there was no significant change in plasma angiotensin II concentration between the two groups. The ratio of renal renin mRNA to β‐actin mRNA in the spirapril‐treated group was higher than that in the control group (P<0.01).

4. At 28 days, plasma renin activity in the spirapril‐treated group was significantly elevated compared with that at 14 days (P<0.05). However, there was no change in renin mRNA between 14 and 28 days after ACE inhibitor administration.

5. Plasma ACE activity in the treatment group was less than that in the control group at any time (P<0.01).

6. Our study demonstrated a non‐proportional change in plasma renin and renal renin mRNA levels. It is suggested that the main determinant of the rate of renin synthesis after administration of an ACE inhibitor may be post‐transcriptional factors, and that unknown mechanisms may be involved in the increase in plasma renin level after long‐term administration of ACE inhibitor in addition to the short feedback mechanism brought about by the decrease in angiotensin II.
A POSSIBLE INTERPRETATION FOR DIFFERENCE IN NEOSTIGMINE‐INDUCED CHANGES OF SPONTANEOUS ACTIVITIES AND EVOKED MUSCLE POTENTIALS BETWEEN RAT MEDIAL GASTROCNEMIUS AND SOLEUS MUSCLES
Authors: Uramoto I. , Watanabe K. , Totsuka T.
Published: June 2007

1. Under urethane‐anaesthesia, changes of spontaneous activities and evoked muscle potentials in rat medial gastrocnemius (MG) and soleus (SOL) muscles induced by the injection of neostigmine were investigated.

2. Before the administration of neostigmine, spontaneous activities were rarely observed and muscle potentials evoked by single shocks were simply biphasic in both MG and SOL muscles. When the anti‐cholinesterase drug was applied, spontaneous discharges of motor units were often observed in bursts in the MG muscles, in contrast to single spikes in the SOL muscles. The biphasic wave of evoked potentials in the MG muscles was followed by one or more oscillations, which were scarcely observed in the SOL muscles. This biphasic wave also occurred even after transection of the sciatic nerve proximal to the stimulating site.

3. A late component with a small amplitude could be observed in the evoked potentials of MG and SOL muscles. It was potentiated in amplitude after the administration of the drug.

4. Prolonged action of acetylcholine (ACh) has been known to occur in the presence of anti‐cholinesterase drugs, and this was taken into account for the mechanism of the phenomena proposed in the present study. Contrasting changes between MG and SOL muscles were observed, which may be explained by different modes of ACh release in the MG and SOL muscles.
SHORT COMMUNICATION: EFFECTS OF NIFEDIPINE AND BAY‐K‐8644 ON THE RELEASE OF CATECHOLAMINES FROM THE DOG ADRENAL GLAND IN RESPONSE TO SPLANCHNIC NERVE STIMULATION
Authors: Takeuchi Akihiko , Kimura Tomohiko , Satob Susumu
Published: June 2007

1. The effects of nifedipine and Bay‐K‐8644 on the release of adrenal catecholamines were examined in anaesthetized dogs.

2. Splanchnic nerve stimulation (SNS) at 1 and 3 Hz produced frequency‐dependent increases in adrenaline (ADR) and noradrenaline (NA) output determined from adrenal venous blood.

3. Neither nifedipine (10 and 30 μg/kg, i.v.) nor Bay‐K‐8644 (10 and 30 μg/kg, i.v.) modified the SNS‐induced increases in catecholamine output. Basal catecholamine output tended to be increased and decreased by nifedipine and Bay‐K‐8644, respectively.

4. Nifedipine produced significant decreases in arterial pressure and renal blood flow rate. Bay‐K‐8644 produced a significant increase in arterial pressure associated with a decrease in renal blood flow rate.

5. These results suggest that dihydropyridine‐sensitive calcium channels do not play a major role in adrenal catecholamine release evoked by SNS.
CROSSOVER COMPARISON BETWEEN THE DEPRESSOR EFFECTS OF LOW AND HIGH WORK‐RATE EXERCISE IN MILD HYPERTENSION
Authors: Tashiro Eiichiro , Miura Shin‐ichiro , Koga Manabu , Sasaguri Manabu , Ideishi Munehito , Ikeda Masaharu , Tanaka Hiroaki , Shindo Munehiro , Arakawa Kikuo
Published: June 2007

1. The relationship between work‐rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial.

2. Ten mild hypertensives were randomly divided into two groups. One group performed low work‐rate exercise (LWE) on a cycle ergometer for 10 weeks (blood lactate threshold; ∼50% of maximum oxygen consumption [V̇O2max]). After a 10 week interval without exercise training, these subjects were then switched to a high work‐rate exercise (HWE) regimen (4 mmol/ L of blood lactate; ∼75% of V̇O2max) for another 10 weeks. In the other group, the order of exercise training was reversed. Since two patients withdrew from the protocol during HWE periods, statistical analysis was performed on the data from the remaining eight patients. There were no order effects observed in any of the data from the two groups.

3. During both LWE and HWE, resting blood pressure (BP) fell significantly after the initiation of exercise therapy (P<0.05). Furthermore, the overall effects of 10 weeks of LWE and HWE on BP were not significantly different.

4. The work‐rate at the lactate threshold, which reflects physical fitness, had increased significantly by 16 W (P<0.01) after the LWE period and by 11 W (P<0.01) after the HWE.

5. During the LWE period, changes in haemodynamic and humoral variables were not significant, except for a reduction in plasma norepinephrine at week 10 (P<0.05). In the HWE period, changes in haemodynamic and humoral variables were not significant.

6. Based on these findings, LWE is recommended for mild hypertensives because of its safety.
ROLE OF SODIUM‐POTASSIUM ATPASE IN PHOSPHATE TRANSPORT BY THE EVERTED SACS OF MOUSE INTESTINE
Authors: Mary P. L. , Rao J. Prakasa
Published: June 2007

1. This study investigated the uptake and release of phosphate from everted intestinal sacs of mice.

2. When the activity of sodium‐potassium ATPase was altered (by changing the cationic concentrations in the medium by the addition of ouabain and the manipulation of metabolism by the use of selective inhibitors or stimulants), the release of phosphate appeared to be much more affected by the changes than the uptake of phosphate.

3. A small sodium gradient allowed uptake to be maintained. The addition of ouabain in the presence of an attenuated gradient significantly reduced the uptake and release of phosphate. The inhibitory effect of ouabain on phosphate release was partly reversed by an increase in the potassium concentration in serosal fluid.

4. These results indicate a role for sodium‐potassium ATPase in phosphate release from the intestine.
DECREASED NOREPINEPHRINE CONTENT IN THE MEDULLA OBLONGATA IN SEVERELY HYPERTENSIVE RATS
Authors: Takami Takeshi , Ito Hiroyuki , Suzuki Tsuneyuki
Published: June 2007

1. To clarify possible abnormalities in catecholamines in the medulla oblongata in relation to severe hypertension, the authors measured changes in catecholamine levels in the medulla oblongata of malignant stroke‐prone spontaneously hypertensive rats (M‐SHRSP). Effects of the adrenal medullae and peripheral nerves were ruled out by adrenal demedullation and chemical sym‐pathectomy.

2. The level of norepinephrine in the medulla oblongata was significantly lower in untreated M‐SHRSP than in untreated WKY (control) rats at 10 weeks of age. Further, it was significantly lower in treated M‐SHRSP than in the treated WKY group at both 6 and 10 weeks of age. The level of epinephrine in 6 week old treated M‐SHRSP was significantly higher than that in age‐matched treated WKY, but no other differences were observed in terms of epinephrine content. There were no age‐ or treatment‐related differences in dopamine levels in the medulla oblongata.

3. Since norepinephrine has an inhibitory effect on blood pressure elevation in the nucleus tractus solitarii (NTS) in the medulla oblongata, the suppression of negative feedback due to a decrease in the activity of inhibitory neurons in the medulla oblongata appears to be involved in the development and progression of severe hypertension in M‐SHRSP.
THE NOVEL MARINE NATURAL PRODUCT PLOCAMADIENE A CAUSES HISTAMINE RELEASE FROM MAST CELLS OF THE GUINEA‐PIG AND RAT IN VITRO
Authors: Thomas Steven G. , Beveridge Andrew A.
Published: June 2007

1. Plocamadiene A is a polyhalogenated monoterpene, (1R, 2S, 4S, 1′E)‐2‐bromo‐l‐chloro‐4‐(2′‐chloroethenyl)‐I‐methyl‐5‐methylenecyclohexane, isolated from red marine algae of the Plocamium genus.

2. This study examined the activity of plocamadiene A on guinea‐pig isolated ileum (GPI) and subsequently on rat isolated peritoneal mast cells.

3. Plocamadiene A (1 μg/mL) produced a slow onset, sustained contraction of the GPI. This was insensitive to atropine (1 μmol/ L) and tetrodotoxin (1 μmol/ L), but was significantly reduced by H1‐histamine receptor antagonists including mepyramine (10 nmol/L), chlorcyclizine (10 nmol/L) and diphenhydramine (0.1 μmol/L). The H2‐histamine receptor antagonists cimetidine (0.1 μmol/L) and ranitidine (10 nmol/L) potentiated the response to plocamadiene A (1 μg/mL).

4. The amplitude of contraction caused by plocamadiene A (1 μg/mL) gradually decreased when the compound was applied repeatedly to the GPI for 5 min every 10 min for 150 min.

5. Contractions to plocamadiene A (1 μg/mL) were reduced to approximately 66% of the time control in ovalbumin‐sensitized GPI challenged with ovalbumin to release endogenous contractile agents.

6. Cromolyn (0.1 mmol/ L) inhibited (by 40%) the response in the GPI caused by plocamadiene A (1 μg/mL) as compared with time controls.

7. Spectrofluorometric assay suggested that both plocamadiene A (10 μg/mL) and compound 48/80 (10 μg/mL) caused histamine release from rat peritoneal mast cells in vitro. This release of histamine was reduced by cromolyn (100 μg/mL).

8. This study concluded that plocamadiene A releases histamine from mast cells of the GPI and peritoneal mast cells in the rat.
RELAXANT EFFECTS OF BRAIN NATRIURETIC PEPTIDE ON GUINEA‐PIG TRACHEAL SMOOTH MUSCLE
Authors: Takagi Kenzo , Araki Nobuyasu
Published: June 2007

1. The relaxant effects of brain natriuretic peptide (BNP) were investigated on guinea‐pig tracheal smooth muscle.

2. Various amounts of BNP (10−9– 10−6 mol/L) showed concentration‐dependent relaxant effects on resting tone, leukotriene D4 (LTD4; 10−8 mol/L) and endothelin‐1 (ET‐1; 10−8 mol/L) induced contraction of tracheal smooth muscle with EC50 values of 3.1± 0.7 ± 10−8, 3.9 ± 1.0 ± 10−8 and 3.5 ± 1.0 ± 10−8 mol/L, respectively.

3. BNP increased tissue cyclic GMP levels in tracheal smooth muscle concentration dependently (187 ± 26 fmol/mg protein in control, 334 ± 77 fmol/mg protein at 10−8 mol/L, 680 ± 54 fmol/mg protein at 10−7 mol/L, 2162 ± 133 fmol/mg protein at 10−6 mol/L).

4. With the addition of BNP, tissue cyclic GMP levels reached a maximum at 1–3 min. The relaxation of tracheal smooth muscle began at 1 min and reached a maximum level at 5 min after the superfusion of BNP (10−6 mol/L). The elevation of cyclic GMP preceded the relaxation of tracheal smooth muscle.

5. These results suggest that BNP may have a potent relaxant effect on tracheal smooth muscle and this effect may be mediated by cyclic GMP level.
ANGIOTENSIN CONVERTING ENZYME INHIBITOR, CAPTOPRIL, INHIBITS CARDIAC HYPERTROPHY WITHOUT CHANGING COLLAGEN TYPES AND CONCENTRATION IN SPONTANEOUSLY HYPERTENSIVE RATS
Authors: Kuzuo Hiroshi , Honda Masaaki , Ishinaga Yuji , Morioka Shigefumi , Tanaka Koichi , Kuramochi Takehiko , Mansoor Abdul M. , Yamori Yukio , Moriyama Katsutoshi
Published: June 2007

1. The effects of the ACE inhibitor, captopril, on collagen metabolism in spontaneously hypertensive rats (SHR) with cardiac hypertrophy was examined. Captopril (100 mg/kg per day) was administered in drinking water to 20 week old male SHR for 12 weeks. Collagen concentration was calculated from hydroxyproline content, and relative proportions of types I, III and V collagen were determined by non‐interrupted SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE). These parameters were examined in age and sex matched Wistar‐Kyoto (WKY) rats, as well as in non‐treated SHR, and compared with those of captopril‐treated SHR.

2. Captopril significantly reduced both blood pressure (191 ± 12.1 vs 146 ± 11.2 mmHg, P < 0.01), and the ratio of left ventricular (LV) weight to bodyweight (BW; 2.38 ± 0.17 vs 2.05 ± 0.12 mg/g, P < 0.01). There were no significant differences in collagen concentration among WKY rats, captopril‐treated SHR and non‐treated 32 week old SHR. However, total collagen content in captopril‐treated SHR reduced significantly compared with non‐treated 32 week old SHR (16.8 ± 2.0 vs 21.3 ± 0.8 mg, P < 0.01). The relative proportion of type V collagen was significantly higher in both captopril‐treated (58.6 ± 3.4 vs 46.8 ± 1.3%, P < 0.01) and non‐treated 32 week old SHR (59.9 ± 3.1 vs 46.8 ± 1.3%, P < 0.01) compared with WKY rats. However, there were no significant differences between captopril‐treated SHR and non‐treated 32 week old SHR.

3. The data from this study showed that captopril reduced cardiac hypertrophy, as reported previously, but did not change collagen types and concentration of the hypertrophied myocardium in SHR.
OXYGEN‐HAEMOGLOBIN DISSOCIATION CURVE IN HYPOXIC RATS OF FIRST OR SECOND GENERATION
Authors: Quatrini U. , Licciardi A. , Morici G.
Published: June 2007

1. Albino Wistar rats were raised in a normobaric hypoxic environment (10% O2 in N2). Two generations of hypoxic rats were observed for changes in their haemoglobin‐oxygen (Hb‐O2) dissociation curves (ODC), 2,3‐diphosphoglycerate (2,3‐DPG), haemoglobin (Hb), and Hill coefficients at P50 (n50). The first generation were called (H1) and the second generation (H2). The control group (N) had a normoxic environment.

2. Thirty‐five rats (13 N rats, 12 H1 rats and 10 H2 rats) were used. The 2,3‐DPG was significantly higher in both hypoxic groups when compared with N rats (2.02 ± 0.51 mmol/L) but 2,3‐DPG of H2 rats was significantly lower than that of H1 rats (H1 = 3.48±0.58 mmol/L and H2 = 2.76±0.54 mmol/L). The haemoglobin values were N = 2.00±0.26, H1 = 2.65±0.32and H2 = 2.36±0.30 mmol/L, respectively.

3. We observed considerable differences in Hb‐O2 affinity between the three groups of rats. In standard conditions (pH = 7.400; pCO2= 40 mmHg at 37°C) the H1 rats showed a significantly decreased Hb‐O2 affinity (P50, st= 37.0 ± 1.3 mmHg) when compared with both H2 and N rats; the H2 rats showed a significantly increased Hb‐02 affinity (P50, st 1 31.1 ± 1.5 mmHg) when compared with controls N (P50, st= 34.7±2.1 mmHg). There were no significant differences in n50 values: N = 2.88 ± 0.44; H1 = 2.88 ± 0.77; and H2 = 2.94 ± 0.67.

4. Therefore, the H1 rats’ ODC was located well to the right of that of N rats; and the H2 rats had an ODC located to the left when compared with both HI and N rats. It is likely that in H2 rats the adaptive processes to the new environment are more advanced; therefore, the magnitude of the compensatory mechanisms required to maintain a sufficient tissue oxygenation may be reduced.
TRANSMEMBRANEIN VITRO AND IN VIVO SODIUM‐LITHIUM COUNTERTRANSPORT IN NEW ZEALAND MAORI
Authors: Maling T. J. B. , van Wissen K. , Siebers R. W. L.
Published: June 2007

1. Erythrocytic sodium‐lithium (Na‐Li) countertransport (CT) was measured in normotensive Maori and non‐Maori by in vitro and in vivo methods to determine its relationship to erythrocytic hypernatraemia previously identified in Maori.

2. In vivo and in vitro CT rates were correlated within race and were similar between races. Countertransport rate was correlated with erythrocytic sodium concentration only in Maori.

3. The findings suggest the possibility of a genetically determined alteration in CT stoichiometry in Maori.
EVIDENCE THAT PRIMARY ALDOSTERONISM MAY NOT BE UNCOMMON: 12% INCIDENCE AMONG ANTIHYPERTENSIVE DRUG TRIAL VOLUNTEERS
Authors: Gordon Richard D. , Ziesak Mary D. , Tunny Terry J. , Stowasser Michael , Klemm Shelley A.
Published: June 2007

1. Six (12%) out of 52 respondents to newspaper advertisements for antihypertensive drug trials had elevated aldosterone to renin ratio, confirmed by repeated measurement.

2. Failure to suppress aldosterone with fludrocortisone acetate administration and oral salt loading confirmed the presence of primary aldosteronism in all six patients.

3. Two of the six patients have already had aldosterone‐producing adenomas removed, one has commenced spironolactone, and one has an adrenal mass on computerized tomography but investigation is incomplete.

4. None of the six patients with primary aldosteronism had unprovoked hypokalaemia.

5. Plasma aldosterone levels did not distinguish those patients with subsequently proven primary aldosteronism from the others. Plasma renin activity (PRA) was a better discriminator, but not as good as the aldosterone to renin ratio.

6. The incidence of primary aldosteronism is probably much higher than the 1% currently quoted in texts, with earlier, normokalaemic forms accounting for the majority of cases.
HUMORAL DETERMINANTS OF Na+ EXCRETION AFTER INTRAVENOUS NaCl LOADING IN NORMAL VOLUNTEERS
Authors: Stokes G. S. , Johnston H. J. , Monaghan J. C.
Published: June 2007

1. Twelve healthy volunteers maintained on a 100 mmol/day Na+ diet, were given an intravenous infusion of 2L saline (0.9%) between 10.00 and 13.00h on 2 study days at least 1 week apart. Urine collections (90 min) were made from 08.30 to 16.00 h. Either carbidopa 100 mg or indomethacin 50 mg was given orally at 07.45 h on one study day and placebo was given on the other (in random order).

2. On the placebo day, saline infusion caused significant decreases in plasma albumin concentration, plasma renin activity (PRA), plasma aldosterone concentration and urinary aldosterone excretion, with 2 to 3‐fold increases in plasma atrial natriuretic peptide (ANP) concentration and urinary dopamine: noradrenaline ratio (DA:NA), whereas mean urinary kallikrein and prostaglandin E2 (PGEI) excretion rates were unchanged. Carbidopa decreased urinary DA:NA and indomethacin decreased urinary PGE2 excretion, compared with the placebo day. Excretion of sodium (Na+) decreased below baseline in two out of six carbidopa‐treated subjects and in three out of six indomethacin‐treated subjects, but showed little or no change in the remainder.

3. These preliminary observations suggest that some subjects in the early phase of natriuresis after an intravenous Na+ load can be identified as having prostaglandin‐dependent or dopamine‐dependent mechanisms for Na+ excretion.
DISSOCIATION OF BLOOD PRESSURE AND ALBUMINURIA IN NORMAL SUBJECTS INFUSED WITH ANGIOTENSIN II AND NORADRENALINE
Authors: Cohen Neale , Phillips Paddy , Gilbert Richard , Jerums George
Published: June 2007

1. Albuminuria is a predictor of diabetic renal disease and atherosclerosis. Changes in blood pressure (BP) may influence albuminuria.

2. The effect of acute BP elevation on albumin excretion rates (AER) using noradrenaline (NA) and angiotensin II (AII) infusions in six normal subjects was examined.

3. The average rise in BP during a 120 min infusion was 23 mmHg for AII and 16 mmHg for NA.

4. There was a marked dissociation between AER and BP levels in both AII and NA infusions.

5. Previously described correlations between BP and AER in ambulatory BP studies may be explained by other factors such as exercise and postural changes.
ANGIOTENSIN‐CONVERTING ENZYME AND REGULATION OF BLOOD PRESSURE IN A LARGE AUSTRALIAN FAMILY
Authors: Summers K. M. , West J. A. , Huggard P. R. , West M. J.
Published: June 2007

1. Animal studies have implicated the angiotensin‐converting enzyme (ACE) gene as an inherited risk factor contributing towards elevation of blood pressure.

2. A polymorphism of the ACE gene, involving the presence or absence of a 287 base pair (bp) segment within the gene region, was assessed for association with high blood pressure in a large, multigeneration Australian family. The association of these alleles with hypertension in unrelated individuals was also examined.

3. There was no evidence to link the ACE gene and high blood pressure in the large family. Similarly, there was no significant association between this gene and high blood pressure in the population tested. As has been reported previously, plasma levels of the enzyme were associated with genotype. These results suggest that this gene is unlikely to be a major risk factor for hypertension in this group.
AGE‐DEPENDENT ALTERATIONS IN VASCULAR SMOOTH MUSCLE CELL RESPONSIVENESS TO PLATELET‐DERIVED GROWTH FACTOR IN GENETIC HYPERTENSION
Authors: Saltis John , Agrotis Alex , Bobik Alex
Published: June 2007

1. This study examined and compared the growth characteristics of vascular smooth muscle cells (VSMC) isolated from 4 and 12 week old spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats following stimulation with platelet‐derived growth factor‐BB (PDGF‐BB).

2. Vascular smooth muscle cells from 4 week old SHR proliferated at a slower rate than VSMC isolated from 12 week old SHR (1.08±0.06/day vs 1.89±0.13/day respectively, P < 0.05). In contrast, there was no difference in the proliferation of VSMC from 4 and 12 week WKY rats (0.62±0.06/day vs 0.82±0.13/day, respectively, P>0.05).

3. The cell density at which VSMC from 4 and 12 week old SHR become refractory to the mitogenic effects of PDGF‐BB was similar and approximately two‐fold greater than VSMC from age‐matched WKY rats.

4. This study concludes that there is an age‐dependent, differential and specific upregulation of growth rate mechanisms in VSMC from SHR which enhance proliferation in response to PDGF‐BB.
VASCULAR SMOOTH MUSCLE CELL PROLIFERATION IN SHR AND WKY RATS: EVIDENCE FOR SPECIFIC DIFFERENCES IN GROWTH INHIBITORY REGULATORY MECHANISMS
Authors: Agrotis Alex , Bray Paula J. , Saltis John , Bobik Alex
Published: June 2007

1. This study examined and compared the actions of transforming growth factor‐β1 (TGF‐β1), heparin, dexamethasone and interferon‐γ on platelet‐derived growth factor‐BB (PDGF‐BB)‐stimulated proliferation of vascular smooth muscle cells (VSMC) from normotensive, Wistar‐Kyoto (WKY) rats and spontaneously hypertensive rats (SHR).

2. Heparin, dexamethasone and interferon‐γ all inhibited VSMC proliferation stimulated by PDGF‐BB in both SHR and WKY rats. There was no difference (P>0.05) in their inhibitory effects, which varied between 40 and 85% for the different agents.

3. Similarly, TGF‐β1 inhibited PDGF‐BB‐stimulated VSMC proliferation in WKY rats by approximately 50%. In contrast, TGF‐β1 potentiated growth factor action on cell proliferation in the SHR by approximately 40%.

4. Specific TGF‐β1‐stimulated regulatory mechanisms involved in the inhibition of proliferation are absent in SHR and this defect may contribute to the vascular hypertrophy which is apparent in genetic hypertension.
ACCURATE DETERMINATION OF THE SIZE OF THE FIRST INTRON DELETION IN THE RENIN GENE OF SHR FROM AN AUSTRALIAN COLONY
Authors: Wang D. Z‐M. , Gregorio‐King C. , Aykut L. , Wilks A. , Morgan T. O. , Nicolantonio R. Di
Published: June 2007

1. It has been reported that the first intron of the renin gene of the spontaneously hypertensive rat (SHR) is shorter than that of the Wistar‐Kyoto (WKY) rat, suggesting a role for this difference in the development of hypertension.

2. The genealogy of some Australian SHR colonies has raised doubts about its similarity to the Japanese, American and European colonies.

3. The polymerase chain reaction (PCR) technique has been used with primers identical to the flanking region of the first intron of the renin gene to determine its length in SHR, WKY and Sprague‐Dawley (SD) from an Australian colony.

4. The size of the first intron of the renin gene in SHR, WKY and SD was found to be approximately 3870, 4550 and 5000 base pairs, respectively, results which agree with those previously published.

5. It was concluded that the first intron deletion, and its size, has been conserved in an Australian SHR colony.
ABNORMALITY OF THE GLOMERULAR ANGIOTENSIN II RECEPTOR IN EXPERIMENTAL DIABETIC NEPHROPATHY
Authors: Makarious M. , Duggan K. , Charlesworth J. A. , Macdonald G. J.
Published: June 2007

1. The combined effect of diabetes and hypertension on the plasma angiotensin II (AII)/glomerular AII receptor (AII‐R) relationship in streptozotocin‐induced diabetes was investigated as well as the effect of glycaemic control on this relationship.

2. Diabetes was induced in spontaneously hypertensive rats (SHR) and Wistar‐Kyoto (WKY) rats with streptozotocin 60 mg/kg and blood sugars maintained between 18–21 mmol/L (uncontrolled diabetes) and 4–8 mmol/L (controlled diabetes). Rats were killed on days 1 and 7. Angiotensin II receptor was estimated by saturation analysis and plasma AII by radio‐immunoassay.

3. Angiotensin II receptors were significantly higher in non‐diabetic SHR than WKY rats (708 ± 62 and 388 ± 36 fmol/mg protein, respectively, P = 0.0008). Plasma AII were comparable in both groups (47 ± 2.7, 38 ± 3.5 pg/mL, respectively) and a significant inverse relationship between AII/AII‐R was observed (WKY P = 0.02 and SHR P = 0.004).

4. On day 7, plasma AII and AII‐R levels in diabetic groups were comparable with those of their non‐diabetic controls. Diabetic WKY rats maintained an inverse correlation between AII and AII‐R (controlled P= 0.04 and uncontrolled P= 0.015), but this did not occur in the SHR.

5. Absence of receptor response to varying ligand concentrations in the diabetic SHR may contribute to the development of nephropathy. Glycaemic control does not appear to reverse this abnormality in the SHR, so that co‐existent hypertension may have a more direct influence on renal function.
NEUROGENIC VASODILATATION IN ISOLATED PERFUSED SEGMENTS OF RABBIT JEJUNAL ARTERY
Authors: La M. , Rand M. J.
Published: June 2007

1. Vasodilator responses were elicited by field stimulation in isolated perfused segments of rabbit jejunal arteries when noradrenergic and purinergic vasoconstrictor responses had been abolished and the smooth muscle partly contracted by endothelin.

2. The stimulation‐induced vasodilator responses were abolished by tetrodotoxin, but were not affected by atropine, propranolol or a nitric oxide synthase inhibitor.

3. After recovery from the vasodilator action of capsaicin, the stimulation‐induced vasodilator responses were greatly reduced or abolished.

4. A competitive antagonist of calcitonin gene‐related peptide (CGRP) blocked vasodilator responses elicited by field stimulation and exogenously administered CGRP.

5. The findings indicated that the mediator of the stimulation‐induced vasodilator responses is neurogenic in origin, and it is not acetylcholine, noradrenaline acting on P‐adrenoceptors, nitric oxide or an endothelium‐dependent vasodilator. It appears to be CGRP, presumably released from sensory nerves in the periarterial plexus.