Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on nociceptive behavior and cardiovascular regulation

Effects of s.c. capsaicin pretreatment on nociception, mean systemic arterial blood pressure, and dose-response curves for depressor effects of substance P (SP) and pressor effects of angiotension II (AII) and norepinephrine (NE) were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Capsaicin pretreatment significantly elevated hot plate and tail flick latencies in SHR subjects but was without effect in WKY rats. Capsaicin pretreatment significantly reduced mean systemic arterial blood pressure in rats of both strains. Both vehicle- and capsaicin-treated WKY subjects exhibited greater depressor responses than did subjects of the corresponding SHR groups after i.v. SP administration. Vehicle-treated SHR subjects exhibited greater pressor responses to both AII and NE than did rats of the vehicle-treated WKY group. Capsaicin treatment decreased the sensitivity of WKY rats to the pressor effects of both AII and NE. Strain differences involving nociception, cardiovascular regulation, and responses to capsaicin may underly the results reported.     

Dopamine receptors mediate cocaine-induced temperature responses in spontaneously hypertensive and Wistar-Kyoto rats.

The involvement of dopaminergic receptors in the responses of conscious, restrained spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats to cocaine was examined using antagonists selective for DA-1 (SCH 23390) or DA-2 (sulpiride) dopamine receptors. Following pretreatment with saline vehicle, SCH 23390 (50 mg/kg, SC), sulpiride (50 mg/kg, IP) or SCH 23390 and sulpiride, cocaine was infused (1.25 mg/kg.min, IV) until death. Cocaine caused an initial pressor and tachycardiac response, which was followed by a progressively developing secondary pressor response. Combined (DA-1 and DA-2) antagonist pretreatment abolished the initial tachycardic response to cocaine. Rectal temperature during cocaine infusion increased in 38.5% of vehicle-treated SHR (designated SHRH), but decreased in the remaining SHR (SHRL) and all vehicle-treated WKY. The time-to-onset of cocaine-induced convulsions (Tc) was reduced in vehicle-treated SHRH compared to vehicle-treated SHRL and WKY. Sulpiride elevated rectal temperature in response to cocaine in SHR and WKY but reduced Tc only in SHR. SCH 23390 abolished hyperthermic responses to cocaine in SHR without altering toxicity in SHR or WKY. Combined pretreatment virtually abolished temperature responses to cocaine in SHR and WKY, but increased the Tc only in WKY. Dopamine receptors, particularly the DA-1 subtype, are involved in cocaine-induced hyperthermia.     

Persistent effects on blood pressure and renal haemodynamics following chronic angiotensin converting enzyme inhibition with perindopril

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats aged 4 and 16 weeks were given an acute oral dose of either Perindopril (3 mg/kg) or vehicle. Direct blood pressure (BP), glomerular filtration rate (GFR) and renal blood flow (RBF) were measured, and renal vascular resistance (RVR) calculated. GFR and RBF were lower in vehicle-treated SHR than WKY at 4 weeks of age, but were not different at 16 weeks. Acute Perindopril increased GFR and RBF and reduced RVR in both strains at both 4 and 16 weeks. Total body sodium, sodium intake and blood pressure were measured in SHR and WKY from 1 to 28 weeks of age. Rats of both strains were treated daily between 4 and 16 weeks of age with either Perindopril (3 mg/kg per day) or vehicle. Chronic Perindopril treatment prevented the development of hypertension in the SHR. From 16 to 28 weeks of age, after stopping Perindopril, BP rose slowly in SHR, but remained lower than vehicle-treated SHR. No changes in total body sodium occurred during Perindopril treatment. GFR and RBF were measured in SHR and WKY chronically treated with either Perindopril or vehicle, 3 days or 12 weeks after stopping treatment. In WKY, GFR and RBF were not different between Perindopril-treated and untreated rats at either measurement. In SHR, GFR and RBF remained significantly higher in rats previously treated with Perindopril at both ages. These findings suggest that renal haemodynamic abnormalities may be important in the initiation of hypertension in the SHR. These renal circulatory abnormalities and the hypertension of the SHR depend, at least in part, on intact converting enzyme activity, yet appear to be independent of abnormalities of total body sodium. At a later age, hypertension seems to develop independently of renal vascular abnormalities.     

Differential behavioral responses of spontaneously hypertensive (SHR) and normotensive (WKY) rats to d-amphetamine

A comparison was made in the behavioral responses of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) normotensive rats to d-amphetamine. Animals were tested at a young age (6 weeks) to minimize the effects of elevated blood pressure on drug responsiveness. SHR rats were more active than WKY rats after injections of 1.0, 2.0, and 4.0 mg/kg d-amphetamine. A significant strain difference in stereotypy was also noted; rearing occurred in SHR rats while lateral or vertical head movements (head waving) occurred in WKY rats. The lack of significant strain differences in the behavioral responses of rats to apomorphine, a direct acting dopamine agonist, suggested that the differential behavioral responses to d-amphetamine were not a result of differences between strains in receptor sensitivity. Pretreatment of rats with reserpine eliminated the strain differences in behavioral responses to d-amphetamine. Pretreatment of rats with alpha-methyl-p-tyrosine prior to administration of d-amphetamine elminated the strain differences in stereotyped behavior; however, WKY rats remained less active than SHR rats. Pretreatment of SHR rats with parachlorophenylalanine had no effect on the behavioral responses to d-amphetamine. In contrast, pretreatment of WKY rats with parachlorophenylalanine resulted in an increase in rearing and a decrease in head waving following an injection of d-amphetamine. These findings suggest that the differences in responses to d-amphetamine of SHR and WKY rats are due in part to variations in the activities of central catecholaminergic and serotonergic neurons.     

Cerebral neuronal activity in spontaneously hypertensive rats as demonstrated by the 14C-deoxyglucose method

Summary The ¹⁴C-deoxy-d-glucose technique was used to examine glucose utilization, as a measure of neuronal activity, in 100 cerebral nuclei by means of radiodensitometry of autoradiographs of serial brain sections. Three groups of rats were studied, namely young spontaneously hypertensive rats (SHR), adult SHR and normal Wistar-Kyoto rats whose blood pressure was acutely increased by injection of angiotensin II.In all three groups as compared to corresponding normotensive controls, glucose utilization was consistently increased in the caudal part of the nucleus (n.) tractus solitarii, medullary related nuclei (n. commissuralis, area postrema and n. dorsalis nervi vagi), n. centromedianus, n. habenulae lateralis, n. supraopticus, n. paraventricularis, n. suprachiasmaticus, n. periventricularis, n. amygdaloideus centralis, and area amygdaloidea anterior. The increase in glucose utilization in these areas is probably due to facilitation of baroreceptor afferent impulses.In young SHR at 4 weeks of age (but not in other groups), increased glucose utilization was found in limbic areas such as the n. interpeduncularis, n. dorso-and ventro-medialis thalami, area anterior and n. dorsomedialis hypothalami, fasciculus medialis telencephali (caudal), n. amygdaloideus lateralis and intercalatus, stria terminalis nuclei, n. dorsalis and intermedius septi, and n. caudatus.In adult SHR at 20 weeks of age (but not in other groups), there was an increase in glucose utilization in the n. intercalatus, n. originis nervi hypoglossi, n. olivaris superior, n. parabrachialis dorsalis and ventralis, substantia grisea centralis, n. paramedianus, reticular formation areas such as n. centralis superior, n. reticulotegmentalis pontis, n. reticularis lateralis and n. tegmentalis pedunculopontinus and substantia reticularis mesencephali, n. corporis mamillaris medialis, n. arcuatus, infundibulum, fasciculus longitudinalis dorsalis and hippocampus ventralis.In SHR at both ages, there was an increase in glucose utilization in most of the sensory trigeminal nuclei, which might indicate enhanced perception of sensory inputs, probably leading to peripheral vasoconstriction. Also in SHR at both ages, increased glucose utilization was found in the substantia nigra pars compacta, n. tegmenti dorsalis and ventralis, fasciculus medialis telencephali (rostral), n. amygdaloideus medialis, n. tractus olfactorii lateralis and n. lateralis septi.In conclusion, baroreceptor-independent neuronal activation in the limbic area in young SHR and in the reticular formation, periventricular fibers and arcuate-infundibular system in adult SHR, in addition to the sensory trigeminal nuclei and tegmental tract at both ages, might be involved in the development and maintenance of hypertension in SHR.     

Comparison of the purinergic contribution to sympathetic vascular responses in SHR and WKY rats in vitro and in vivo

Isolated tail arteries from spontaneously hypertensive rats (SHR) were more responsive than those from Wistar-Kyoto (WKY) control rats to exogenously applied noradrenaline (NA), ATP, alpha,beta-methylene ATP (mATP), KCl and sympathetic nerve stimulation. The sympathetic contractile responses of the SHR and WKY were both reduced to 10-20% of control by alpha 1-adrenoceptor antagonism. The pressor responses to sympathetic nerve stimulation were significantly greater in the SHR than the WKY rats at all stimulation frequencies examined (1-10 Hz). There was no significant difference between SHR and WKY rats in the magnitude of pressor responses produced by i.v. administration of NA or mATP. The pressor responses to sympathetic nerve stimulation in the pithed SHR were no more resistant to alpha-adrenoceptor antagonism than those of the WKY. The results suggest that the contribution by ATP to sympathetic vasoconstriction is no greater in SHR than WKY.     

Differential amino acid transmission in the locus coeruleus of Wistar Kyoto and spontaneously hypertensive rats

In addition to differences in their blood pressure, Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) are known to differ in their emotional behaviour. The neurochemistry underlying these differences is not well understood. In the present study the release rates of the two main regulatory amino acids in the locus coeruleus, glutamate and gamma-aminobutyric acid (GABA), were monitored in WKY rats and SHR to investigate whether basal and/or challenged neurotransmission differs between these strains. The strains differed in their basal blood pressure (WKY 102±2 mmHg, SHR 140±4 mmHg), as well as in their emotional behaviour, since WKY rats displayed enhanced anxiety-related behaviour in the open field test (time in centre: WKY 197±40 s/30 min, SHR 741±93 s/30 min). Basal glutamate and GABA release rates did not differ between WKY rats and SHR. A rise in blood pressure induced by intravenous infusion of noradrenaline for 10 min enhanced GABA release in WKY rats by 60%, while no effect was observed in SHR. Glutamate release did not respond to experimental hypertension in both strains. Intravenous infusion of sodium nitroprusside led to a fall in blood pressure, which was less pronounced and was of shorter duration in WKY rats than in SHR. The depressor response had no effect on amino acid release in the locus coeruleus of both strains. Mild stress induced by noise or tail pinch led to slight rises in arterial blood pressure (10 mmHg and 20 mmHg respectively), which were similar in WKY rats and SHR. Tail pinch enhanced the release rates of glutamate and GABA in the locus coeruleus of WKY rats and SHR; however, no strain differences were noted. Noise stress did not significantly influence amino acid release. These findings demonstrate that SHR and WKY rats differ in GABAergic neurotransmission, which is revealed in response to specific cardiovascular challenges, but not to mild stressors. The observed lack of GABA response to blood pressure elevation in SHR may reflect a disturbed mechanism counteracting high blood pressure, possibly contributing to hypertension in this strain.     

The abnormal renal vasodilator response to D1-like receptor stimulation in conscious SHR can be normalized by AT1 blockade

BACKGROUND: We previously showed that the renal vasodilator response to a D1-like receptor agonist is blunted in conscious SHR compared with WKY rats. The mechanism of this impaired dopaminergic responsiveness in SHR is unclear. An altered balance between the renin-angiotensin-aldosterone system (RAAS) and the dopaminergic system may be involved. To determine the interaction between the RAAS and the dopaminergic system in the blunted D1-like responsiveness in SHR, we studied the renal vasodilator response to the D1-like receptor agonist fenoldopam before and after 7 days of pretreatment with the AT1-receptor antagonist (AT1-A) L158,809 in conscious SHR and WKY rats. METHODS: Effective renal plasma flow (ERPF) was measured by the clearance of I-hippuran. Mean arterial pressure (MAP) was measured via an intraarterial catheter. RESULTS: Without pretreatment, MAP was reduced to comparable degrees by fenoldopam in WKY (-7 +/- 4%, ns) and SHR (-6 +/- 1%, P < 0.05). However, ERPF was significantly more increased (P < 0.006) by fenoldopam in WKY (+26 +/- 2%, P < 0.0001) than in SHR (+2 +/- 2%, ns). AT1-A treatment reduced MAP and increased ERPF and glomerular filtration rate significantly in both strains. Pretreatment with AT1-A significantly potentiated the fenoldopam-induced rise in ERPF in SHR, but not in WKY, without affecting the blood pressure responses in either strain. As a result, during pretreatment with an AT1-A, the rise in ERPF by fenoldopam was similar in both strains (SHR +25 +/- 2%, P < 0.0001; WKY +33 +/- 2%, P < 0.0001). CONCLUSIONS: These results suggest that the RAAS accounts for the blunted renal vasodilator response to a D1-like receptor agonist in SHR. A dysbalance between the dopaminergic system and the RAAS may be involved in the abnormal renal hemodynamic regulation in SHR.     

Effect of sodium depletion on the release of [3H]norepinephrine from central and peripheral tissue of Wistar-Kyoto and spontaneously hypertensive rats

To study the relationship between sodium intake, the sympathetic nervous system, and hypertension, we studied the effects of a 7-9 day dietary restriction of sodium in three different ages of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Field-stimulated [3H]norepinephrine ( [3H]NE) release was measured in portal vein, anterior hypothalamus, and the A2 region of the nucleus tractus solitarius (NTS) of 5- to 6-, 10- to 11-, and 28- to 30- week-old SHR and age-matched WKY. A low-sodium diet (0.05% Na+, control 0.5% Na+) significantly lowered stimulated [3H]NE release from portal vein and anterior hypothalamus in SHR and WKY at all three ages. However, release from the A2 region was not altered by sodium restriction. The results of the present study suggest that lowered dietary sodium can selectively alter norepinephrine release in both the peripheral and central sympathetic nervous system of SHR and WKY. The results also suggest that the SHR at 5-6 weeks are more sensitive to altered dietary sodium than are age-matched WKY.     

Adrenomedullary and beta-adrenergic participation in enhanced sympathetic pressor responses of spontaneously hypertensive rats

The beta-adrenergic and adrenomedullary components of pressor responses to sympathetic nerve stimulation were studied in spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). The effects of electrical stimulation of the entire spinal cord of pithed rats pretreated with tubocurarine and atropine were studied on systolic blood pressure, heart rate and plasma cyclic AMP levels. The heart rate increase upon low frequency stimulation (1 Hz) and the blood pressure elevation upon stimulation at higher frequencies (3 and 5 Hz) were higher in SHR than in WKY whereas the increase in circulating cyclic AMP level was not different in the two strains. Pretreatment with propranolol (2.5 mg X kg-1) further enhanced the pressor responses in SHR but not in WKY, although it inhibited the heart rate acceleration and decreased the circulating level of cyclic AMP similarly in the two strains. After acute adrenalectomy, the elevations of blood pressure and circulating cyclic AMP levels were reduced to an identical level in SHR and WKY. These results show that the marked enhancement of the pressor response observed in SHR upon stimulation of the entire sympathetic outflow is mostly of adrenomedullary origin and includes a hypotensive component due to beta-adrenoceptor stimulation which is not present in WKY.     

前阿黑皮原和强啡肽原基因在自发性高血压大鼠脑内的表达

目的：检测前阿黑皮原（ＰＯＭＣ）和强啡肽原（ＰＰＤ）基因在高血压（ＳＨＲ）和同龄Ｗｉｓｔａｒ－Ｋｙｏｔｏ大鼠（ＷＫＹ）中的表达。方法：用地高辛（ＤＩＧ）标记的ＲＮＡ探针进行原位杂交检测ＰＯＭＣ ｍＲＮＡ和ＰＰＤ ｍＲＮＡ。 结果：ＰＯＭＣｍＲＮＡ６主要表达于弓状核，而ＳＨＲ表达量大于ＷＫＹ。ＰＰＤ ｍＲＮＡ表达于海马、下丘脑、中脑中央灰质、孤束核、胸髓。在齿状回、孤束核、内侧视前区，ＳＨＲ ＰＯ     

Age-Related decrease in calcitonin gene-related peptide mRNA in the dorsal root ganglia of spontaneously hypertensive rats

Age-related changes in levels of calcitonin gene-related peptide (CGRP) mRNA of the dorsal root ganglia was studied in 8-, 12- and 15-week-old spontaneously hypertensive rats (SHR) and age-matched normotensive Wistar Kyoto rats (WKY). CGRP mRNA levels in SHR but not in WKY decreased with age. The contents of CGRP-like immunoreactivities in the atrium and mesenteric artery of 15-week-old SHR were greater than those in age-matched WKY. These results suggest that the outflow of CGRP-containing nerves from the spinal cord and CGRP release from CGRP nerve terminals decreases in SHR.     

EFFECT OF DELAPRIL ON THE VASCULAR ANGIOTENSIN II RELEASE IN ISOLATED HIND LEGS OF THE SPONTANEOUSLY HYPERTENSIVE RAT: EVIDENCE FOR POTENTIAL RELEVANCE OF VASCULAR ANGIOTENSIN II TO THE MAINTENANCE OF HYPERTENSION

1. In view of a recent interesting hypothesis that the vascular renin-angiotensin system (RAS) plays an important role in the maintenance of hypertension, we examined the effect of delapril (DP), a newly developed angiotensin converting enzyme inhibitor (ACEI), on angiotensin II (Ang II) release from isolated perfused hind legs of spontaneously hypertensive rats (SHR) in comparison with normotensive rats of Wistar-Kyoto strain (WKY). 2. Male SHR and WKY were given DP orally (10 mg/kg per day) for 2 weeks. Isolated hind legs of these rats were perfused with angiotensinogen-free Krebs-Ringer solution, and Ang II released into the perfusate was determined directly by extraction with Sep-Pak C18 cartridges connected to the perfusion system. 3. Delapril produced a sustained antihypertensive action in SHR but not in WKY. The spontaneous release of Ang II in SHR was 112.9 +/- 17.6 pg during the first 30 min of perfusion, which was somewhat greater than that in WKY (96.5 +/- 9.8 pg). An active metabolite of DP, delapril diacid (DPD), when added to the perfusion medium, suppressed the Ang II release in a dose-dependent manner in the two strains. Oral pretreatment of DP for 2 weeks suppressed the Ang II release by 60% in WKY and more pronouncedly by 73% in SHR. 4. These results suggest the presence of a functional RAS in vascular tissues which contributes to the maintenance of vascular tone of SHR, and that ACEI including DP exerts their antihypertensive effect through inhibition of vascular Ang II release in this animal model of human hypertension.     

Mechanisms underlying biochanin A-induced relaxation of the aorta differ between normotensive and hypertensive rats

1. The aim of the present study was to investigate the mechanism underlying biochanin A-induced relaxation of the aorta in spontaneously hypertensive rats (SHR). 2. The tension in isolated ring preparations of thoracic aortas from normotensive (Wistar-Kyoto (WKY) rats) and SHR at 5 and 10 weeks of age was measured isometrically. 3. Biochanin A (10(-7) to 10(-4) mol/L) induced a concentration-dependent relaxation in aortic rings from both strains at the age of 5 and 10 weeks and the relaxation was greater in rings from 10-week-old SHR compared with age-matched WKY rats. The vasorelaxation induced by biochanin A was significantly reduced by denudation of the endothelium in aortic rings from SHR, but not WKY rats. Treatment with either indomethacin, a cyclo-oxygenase inhibitor, or N(omega)-nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, had little effect on the relaxation induced by biochanin A in aortic rings from either strain. Glibenclamide, a selective inhibitor of ATP-sensitive potassium channels, significantly attenuated the relaxation induced by biochanin A in aortic rings from both strains, although the extent of reduction was greater in WKY rats than SHR. Conversely, treatment with 4-aminopyridine, a selective inhibitor of voltage-dependent potassium channels, or tetraethylammonium, an inhibitor of calcium-activated potassium channels, significantly reduced the vasorelaxation induced by biochanin A in rings from SHR but not WKY rats. 4. The greater vasorelaxation produced by biochanin A in aortic rings from 10-week-old SHR is endothelium dependent. Different mechanisms underlie the relaxant effects of biochanin A in aorta from SHR and WKY rats. The mechanisms of biochanin A-induced vasorelaxation in thoracic aortas from both normotensive and hypertensive rats involve ATP-sensitive potassium channels and, in addition, in rings from the hypertensive strain at 10 weeks of age, an endothelium-derived activation of smooth muscle cell potassium channels contributes to the vasorelaxation observed.     

Decreased postsynaptic dopaminergic and cholinergic functions in the ventrolateral striatum of spontaneously hypertensive rat

Dopamine and acetylcholine receptor functions in spontaneously hypertensive rats (SHR) and in control progenitor Wistar-Kyoto (WKY) rats were assessed, using dopamine D1-like/D2-like receptor-mediated and acetylcholine receptor-mediated jaw movements as readout parameters. Spontaneous behaviours such as locomotor activity, vacuous chewing, grooming, sniffing and rearing occurred significantly more in SHR than in WKY rats. In the anaesthetised rats, a mixture of SKF 38393 (5 micrograms), a dopamine D1-like receptor agonist, and quinpirole (10 micrograms), a dopamine D2-like receptor agonist, readily produced repetitive jaw movements in WKY rats, but not SHR, when bilaterally injected into the ventrolateral striatum; such injections into the nucleus accumbens shell were ineffective in each strain. Bilateral injections of carbachol (2.5 micrograms each side), an acetylcholine receptor agonist, into the ventrolateral striatum elicited repetitive jaw movements in both SHR and WKY rats, but to a far less degree in SHR. The present study demonstrates that spontaneous behaviours are enhanced in SHR, and that postsynaptic dopamine D1-like/D2-like receptors and acetylcholine receptors in the ventrolateral striatum of SHR are hyposensitive when compared to those of WKY rats.     

THE INFLUENCE OF AGE AND SEX ON CARDIAC,RENAL AND CAUDAL ARTERY CATECHOLAMINE CONTENT IN SPONTANEOUSLY HYPERTENSIVE (SHR) AND WISTAR KYOTO (WKY) RATS

• 1 Noradrenaline (NA), adrenaline (A) and dopamine (DA) levels were measured in the heart, kidney and caudal artery of male and female SHR and WKY rats aged 6, 14 and 28 weeks, and the influence of strain, sex and age on catecholamine content determined.
• 2 Levels of A were elevated in all three regions of SHR compared to WKY rats, independent of age and sex. This may represent increased A accumulation in sympathetic nerves resulting from the increased sympatho-adrenomedullary hyper-reactivity of the SHR strain.
• 3 DA levels were also elevated in the heart and kidney of SHR rats, independent of sex and age.
• 4 NA levels were lower in the heart of SHR rats, but this appeared to be partly a consequence of cardiac hypertrophy and partly due to strain differences between older male but not female rats. Thus a simple association between decreased cardiac NA levels and hypertension appeared unlikely.
• 5 It is emphasised that further genetic studies of F₂ backcross rats would be required to establish an etiological association between these differences in catecholamine levels and differences in blood pressure between the SHR and WKY strains.

     

Capsaicin-sensitive vagal afferent fibers and stimulation of gastric acid secretion in anesthetized rats

The sensory neurotoxin, capsaicin, has been used to study the reflex pathway by which gastric acid secretion increases in response to gastric distension in urethane-anesthetized rats. Capsaicin (1%) or vehicle (10% Tween 80 in olive oil) was applied directly to each cervical vagus 7-14 days prior to experiments. Gastric acid secretion was measured in acute gastric fistula rats by continuous intragastric perfusion and back titration or by flushing the gastric contents with saline every 10 min. Gastric acid secretion was stimulated by distension (5 ml for 6 min) or by injection of secretagogues (histamine 5.0 mg/kg s.c., bethanechol 0.5 mg/kg s.c. or pentagastrin 16 micrograms/kg per h i.v.). Gastric distension increased gastric acid secretion 6.2 times over basal gastric acid secretion in vehicle-treated control rats; capsaicin pretreatment significantly reduced this response by 40%. Bilateral cervical vagotomy significantly reduced the secretory response to gastric distension in the vehicle-treated group to a level not significantly different from capsaicin-treated rats. The secretory response to histamine was reduced by 42% in capsaicin-treated rats compared to vehicle pretreatment whereas the responses to pentagastrin and bethanechol were unaltered. These results indicate that capsaicin-sensitive vagal afferent fibers mediate the vagal portion of the secretory response to gastric distension; in addition these afferents play a role in the gastric acid secretory response to histamine.     

NERVE GROWTH FACTOR mRNA CONTENT PARALLELS ALTERED SYMPATHETIC INNERVATION IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. In order to explore the mechanisms responsible for the hypernoradrenergic innervation of the vasculature in the spontaneously hypertensive rat (SHR) the tissue content of nerve growth factor messenger ribonucleic acid (NGFmRNA) was examined. 2. The concentration of NGFmRNA was markedly elevated in mesenteric veins obtained from SHR when compared with the contents of NGFmRNA in veins from Wistar Kyoto rats (WKY). 3. The NGFmRNA content of kidneys was greater in SHR when compared with the levels present in WKY rats for 10- and 43-day-old animals. 4. In contrast to the pattern observed for veins and kidneys, the NGFmRNA content of SHR hearts was smaller than those present in hearts from WKY rats for 2, 10 and 43-day-old animals. 5. The results demonstrate that tissues with enhanced innervation (the kidney and mesenteric vasculature) in SHR are associated with an enhanced expression of NGFmRNA. In contrast, the heart, which does not display an enhanced sympathetic innervation in the SHR, does not have an increased expression of NGFmRNA. 6. It is suggested that in the SHR there is a tight relationship between hypernoradrenergic innervation in the vasculature and gene expression for NGFmRNA.     

HYPOTENSIVE ACTIVITY OF AQUEOUS EXTRACT OF ANDROGRAPHIS PANICULATA IN RATS

1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood presure (SBP) of spontaneously hypertensive rats (SHR). 2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by thiobarbituric acid (TBA) assay. 3. The extract significantly lowered the SBP of both SHR and WKY rats. 4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls. 5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract-and vehicle-treated WKY rats. 6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.     

Age-dependent Modifications of the Role of Prostanoids in Cardiac Preparations from Normotensive and Hypertensive Rats

The cardiac response to field stimulation of adrenergic nerve terminals in isolated atrial preparations from adult (6-month-old) normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SH) rats was enhanced in comparison to that observed in the atrial tissue of young (2-month-old) animals of both strains; the increase in the sympathetic response was significantly higher in preparations from SHR than in those from age-matched WKY rats. The sensitivity of cardiac adrenergic neurotransmission to the prejunctional inhibitory effects exerted by exogenously administered prostaglandin E₂ (0.1 nM-1 μM) and iloprost (0.1-10 μM) did not show any strain-dependent difference in preparations from both young and adult rats. Moreover, acetylsalicylic acid (500 μM) induced a similar degree of potentiation of the response to sympathetic stimulation in atrial tissues of young WKY and SH animals; however, the effect of the cyclo-oxygenase inhibitor was completely missing in preparations from adult rats of both strains. Finally, arachidonic acid (10 μM) inhibited the adrenergic response to a greater extent in preparations from young and adult SH rats than in those from agematched normotensive rats. The results of the study indicate that, at least in cardiac preparations, changes in the modulatory role of endogenous prostaglandins occur as age-dependent processes and, therefore, may not be indicative of possible differences in the role of prostaglandins between hypertensive and normotensive animals. The possible significance of the dissimilar response to arachidonic acid, detected as the only difference between preparations from SH and WKY rats, is discussed.