PLASMA AND PITUITARY PROLACTIN AND BLOOD PRESSURE IN BROMOCRIPTINE-TREATED SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

1. The effects on blood pressure (BP) and plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine delivered by osmotic minipump were investigated in spontaneously hypertensive rats (SHR) and their normotensive controls, the Wistar-Kyoto rats (WKY). 2. In the SHR, a fall in BP which was steepest over the initial few days and sustained up to day 12 was observed in the bromocriptine-treated group compared with the lack of a change in BP observed in the vehicle-treated group. The plasma PRL level taken on day 13 was found to be significantly lower in the bromocriptine-treated group than in the vehicle-treated group. 3. In the WKY, bromocriptine had no significant effect on either BP or plasma PRL. 4. Pituitary PRL content was significantly lower in the SHR than in the WKY. The suppression by bromocriptine treatment was greater in the SHR than in the WKY. 5. These results provide further evidence for a central dopaminergic insufficiency in the SHR and raise the possibility that PRL may, either directly or indirectly by interacting with other factors in the SHR, influence BP.     

EFFECT OF AN ANTIHYPERTENSIVE DRUG ON BRAIN ANGIOTENSIN II LEVELS IN RENAL AND SPONTANEOUSLY HYPERTENSIVE RATS

1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain All. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma All in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two-kidney, one-clip (2K1C) and spontaneously hypertensive (SHR) rats. 2. Hydralazine (20mg/kg per day) and vehicle (water) were given to 2K1C rats between 2 and 6 weeks after operation and SHR for 4 weeks. In addition, vehicle was applied to sham operated rats and Wistar-Kyoto (WKY) rats. Brain and plasma AII was measured by a highly sensitive radioimmunoassay coupled with high performance liquid chromatography. 3. Hydralazine treatment effectively lowered blood pressure to the same levei of sham-operated and WKY rats. 2K1C rats showed significantly higher plasma All than sham rats, but hydralazine treatment did not show any change in plasma AII. Brain AII in the hypothalamus region of 2K1C rats showed a significantly higher level than sham rats. Interestingly, hydralazine treatment diminished this increase in brain AII. In contrast, SHR showed higher brain A11 levels in the hypothalamus, brainstem and cerebellum than in WKY rats, whereas there was no significant change in plasma AII concentration between SHR and WKY rats. In contrast to the results found in 2K1C rat experiments, hydralazine treatment failed to decrease brain AII levels despite lowered blood pressure. 4. In conclusion, brain AII is affected by systemic blood pressure in 2K1C hypertensive rats, but not in SHR, and the mechanisms which cause the difference between 2K1C rats and SHR are unknown in this study.     

PATHOGENETIC ROLE OF VASCULAR ANGIOTENSIN-CONVERTING ENZYME IN THE SPONTANEOUSLY HYPERTENSIVE RAT

1. This study was undertaken to examine the possibility that the level of angiotensin-converting enzyme (ACE) increases in vascular tissue, and that this may participate in the pathogenesis of hypertension in spontaneously hypertensive rat (SHR). 2. In SHR, at the established hypertensive stage, the prolonged antihypertensive effect induced by a single oral dose of spirapril was closely correlated to the long-lasting inhibition of ACE in aortae and mesenteric arteries. In contrast, ACE in plasma, lung, heart and kidney recovered from inhibition faster than in vessels. 3. Prolonged daily oral treatment of SHR with spirapril, initiated at the age of 8 weeks and continued for 8 weeks, prevented the development of hypertension with concomitant decrease in aortic ACE activity. Blood pressure continued to be suppressed after the drug was withdrawn, as did the aortic ACE activity. 4. Spontaneously hypertensive rats developed hypertension with age as well as with the increase in aortic ACE activity which became higher with age than that of Wistar-Kyoto (WKY) normotensive control rats. On the contrary, ACE activity in plasma and lung of SHR was substantially lower than that of WKY at any age from 4 to 20 weeks old. Brain ACE activity of SHR did not differ from that of WKY at any age. Aged SHR showed the lower enzyme activity in the kidney compared with that of age-matched WKY. 5. Our results support the hypothesis that increased vascular ACE may play an essential role in the development and maintenance of hypertension in SHR.     

Cilazapril prevents hypertension in spontaneously hypertensive rats

Chronic daily administration of cilazapril (1 X 10 mg/kg/day p.o., from age 4 to 14 weeks) to young spontaneously hypertensive rats (SHR) prevented the development of hypertension. The antihypertensive effect of a single dose of cilazapril persisted greater than 24 h. Discontinuation of long-term treatment resulted in an increase of systolic arterial blood pressure (SAP) to control hypertensive levels within 4 days. Following 10 weeks of drug administration, comparative hemodynamic studies were carried out on age-matched (14 weeks) control SHR and cilazapril-treated SHR. Cilazapril-treated SHR had a significantly lower mean arterial blood pressure (MAP) and total peripheral vascular resistance than did control SHR. The antihypertensive effect of cilazapril was not associated with changes in heart rate (HR). The myocardial performance parameters, cardiac output, and stroke volume, were similar in treated and control SHR, suggesting that the antihypertensive effect of cilazapril following chronic administration to SHR is mainly due to a reduction in peripheral vascular resistance. Vasopressor responses to angiotensin I were significantly lower in cilazapril-treated SHR than in control SHR. By contrast, pressor responses to angiotensin II and a high dose of norepinephrine (1.0 microgram/kg i.v.) were significantly enhanced. Isoproterenol elicited a fall in blood pressure in both groups, the extent of which was dependent upon the magnitude of basal blood pressure levels. Chronic cilazapril treatment resulted in a reduction of heart weight, suggesting that the drug may prevent development of cardiac hypertrophy in SHR. Kidney and adrenal weights were unaffected by the chronic treatment. Specific renin activities (SRA) in tissues of SHR were increased by factors of 20 (plasma) or 2 (kidney and adrenal) following cilazapril administration.(ABSTRACT TRUNCATED AT 250 WORDS)     

红花黄素对高血压大鼠的降压作用及对肾素-血管紧张素的影响

Safflower yellow (SY) is a mixture of chalconoid compounds extracted from Carthamus tinctorius L. Ig SY 1～2 g·kg^-1·d^-1lowered the blood pressure of spontaneously hypertensiverats (SHR), for about 1.86～3.86 kPa. Five weeks after administration of SY, the plasma renin ac-tivity and angiotensin Ⅱ level diminished in the SHR experimental groups. These suggest that the de-crease of blood pressure is mediated by the renin-angiotensin system.     

CHARACTERIZATION OF THE BARORECEPTOR HEART RATE REFLEX DURING DEVELOPMENT IN SPONTANEOUSLY HYPERTENSIVE RATS

1. We have examined the baroreceptor-heart rate (HR) reflex in weight-matched conscious spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats during development. 2. Graded steady-state changes in mean arterial pressure (MAP) and the corresponding HR responses before and after vagal blockade with methylatropine were fitted to an S-shaped logistic function. 3. At 6 weeks of age, SHR had a 17% higher MAP than WKY and an increased baroreflex gain (slope) compared with WKY due to an increased curvature of the MAP-HR relationship. The HR range (the difference between the upper and lower HR plateaus) was similar in the two strains at this time. 4. From 9-14 weeks of age, the baroreflex gain progressively increased in WKY and decreased in SHR due to corresponding alterations in HR range. 5. By 20 weeks the baroreflex gain was 23% lower in SHR than WKY due to a 37% lower HR range. 6. There were no differences between the two strains in the sympathetic component of the baroreflex at any age, suggesting that the changes to baroreflex properties were confined to the cardiac vagus. 7. Pretreatment with enalapril from 4-9 weeks reduced the hypertension of SHR at 14 and 20 weeks by 38% and abolished all baroreceptor-HR reflex differences between the two strains. 8. These studies suggest that the major alteration to the baroreceptor-heart rate reflex in the SHR during development was a reduction in the maximum vagal capacity to respond to changes in blood pressure. This effect developed after the onset of hypertension and was prevented by antihypertensive treatment early in life. The lack of effect on the cardiac sympathetic component suggests that altered arterial baroreceptor afferents are not unlikely to be responsible.     

EFFECT OF TEMOCAPRIL ON HAEMODYNAMIC AND HUMORAL RESPONSES TO EXERCISE IN PATIENTS WITH MILD ESSENTIAL HYPERTENSION

1. This study was carried out to evaluate the effect of temocapril on haemodynamic and humoral responses to exercise in nine patients with mild essential hypertension (WHO stages I and II). 2. After a 4-week placebo period, temocapril was administered at a dose of 1.0 mg once daily for 2–4 weeks. Graded submaximal bicycle ergometer exercise was performed before and after temocapril treatment, and the changes in arterial blood pressure, heart rate, cardiac output (CO), and systemic vascular resistance (SVR) were evaluated. In addition, the plasma norepinephrine (NE) level was determined both at rest and peak exercise before and after temocapril treatment. 3. Both the systolic and diastolic blood pressure were reduced at rest and during exercise by temocapril treatment. No significant change in the resting heart rate and CO was observed, and the exercise-induced increase of these parameters was also not affected by temocapril. In contrast, the resting SVR was significantly decreased by temocapril, although the exercise SVR was similar during both temocapril and placebo treatment. 4. Although there was no significant change in the plasma NE level with temocapril treatment, the exercise-induced increase of plasma NE was significantly suppressed by temocapril. 5. These results indicate that temocapril reduces the blood pressure without causing any significant changes in the heart rate and CO at rest, and that it does not produce any changes in the haemodynamic response to exercise.     

TRANSPLANTATION STUDIES OF THE ROLE OF THE KIDNEY IN LONG-TERM BLOOD PRESSURE REDUCTION FOLLOWING BRIEF ACE INHIBITOR TREATMENT IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

1. Brief treatment with angiotensin-converting enzyme (ACE) inhibitors in young spontaneously hypertensive rats (SHR) causes a persistent reduction in blood pressure associated with a relatively selective reduction in renal vascular resistance. 2. To study the possible role of the kidney in this long-term hypotensive effect, we transplanted kidneys from untreated SHR into SHR that had been treated with perindopril (3 mg/kg per day) between 6 and 10 weeks of age and also transplanted kidneys from perindopril-pretreated SHR into untreated SHR. After transplantation, the remaining native kidney was removed so that only donor kidneys remained. 3. Untreated SHR that received kidneys from perindopril-pretreated SHR showed an initial fall in blood pressure followed by a rapid increase in pressure, weight loss and early death. 4. The transplantation of kidneys from control SHR into perindopril-pretreated SHR resulted in a rise in blood pressure that obviated the long-term reduction seen normally in these animals. 5. Kidneys from perindopril-pretreated SHR may be susceptible to the high blood pressure in untreated SHR. 6. The blood pressure increase in perindopril-pretreated SHR that accompanies substitution of the native kidneys by kidneys from untreated SHR further supports the hypothesis that the kidney is responsible for the long-term pressure effects following ACE inhibition in young SHR.     

THE EFFECT OF DIETARY FISH OIL AND LONG-TERM SALT LOADING ON BLOOD PRESSURE AND EICOSANOID METABOLISM IN SPONTANEOUSLY HYPERTENSIVE RATS

1. Dietary suppression of prostanoid synthesis with fish oils has had little effect on blood pressure in models of experimental hypertension in rats. However, a pressor effect of dietary fish oils was observed in spontaneously hypertensive rats (SHR) subject to 1 week of salt loading. 2. Animals were allocated to semisynthetic diets containing either 10% by weight Max EPA fish oil or a control diet of coconut oil, and studied after receiving 1.5% saline for 4 weeks. 3. Within the first week of salt loading, SHR-fed fish oil showed an increase in blood pressure (mean = 9 mmHg) relative to controls. This effect was transient, and after the first week of salt loading there was little difference in blood pressure between the two dietary groups. 4. Following dietary treatment there were substantial changes in plasma fatty acid composition with a 48% decrease in arachidonic acid content of fish oil-fed rats compared with control animals. Rats on the fish oil diet showed a threefold decrease in serum thromboxane generation. Prostacyclin production by incubated segments of aorta was reduced by more than 50% compared with the coconut oil-fed control group. 5. SHR on the fish oil diet showed increased urine volume and sodium excretion, presumably due to increased fluid and salt intake. 6. This study shows that dietary suppression of prostacyclin synthesis is associated with only a minor effect on blood pressure in long-term salt loading of SHR.     

EFFECT OF PARATHYROIDECTOMY ON DEVELOPMENT OF HYPERTENSION AND ATRIAL RESPONSIVENESS IN SPONTANEOUS HYPERTENSIVE RATS

1. In order to further clarify the relationships between parathyroid function and development of hypertension, the effects of parathyroidectomy (PTX) on blood pressure and on responsiveness of atria isolated from spontaneous hypertensive rats (SHR) were examined. 2. PTX was carried out in 6-week-old SHR and normotensive Wistar rats. The experiments were performed 2 weeks after surgery. 3. PTX reduced the plasma calcium concentration and decreased atrial calcium content in SHR. On the other hand, basal contractile force and beat frequency of isolated atria were higher in PTX SHR than in sham-operated SHR. In response to cumulative addition of isoprenaline, atria from PTX SHR displayed diminished inotropic and chronotropic responses compared with sham-operated SHR. Similar results were obtained in atria isolated from Wistar rats. When calcium sensitivity was studied in atria from Wistar rats, basal and isoprenaline-induced maximum contractile forces were higher in PTX group than in the sham-operated group. Nevertheless, basal and isoprenaline-induced maximum contractile forces, determined at the respective plasma ionized calcium concentration of PTX and sham-operated groups (0.83 and 1.22 mmol/L), were not significantly different. 4. Our results do not favour a role for alteration in atrial activity as a causal mechanism in delayed development of experimental genetic hypertension after parathyroidectomy.     

Bromocriptine-induced decrease in blood pressure in conscious spontaneously hypertensive rats: evidence for a peripheral site of action

The aim of the study was to discover whether the dopamine agonist bromocriptine has a central or peripheral site of action on blood pressure. An intraperitoneal injection of bromocriptine (0.5 mg kg-1) induced a long-lasting decrease in blood pressure in conscious spontaneously hypertensive rats (SHR). This effect was blocked by peripheral pretreatment with haloperidol or domperidone, but not by central treatment with haloperidol. A central injection of bromocriptine had only minor effects on blood pressure. These results suggest that primarily peripheral, rather than central, mechanisms are involved in the hypotensive effects of bromocriptine.     

VASCULAR SMOOTH MUSCLE POLYPLOIDY IN THE DEVELOPMENT AND REGRESSION OF HYPERTENSION

1. Two groups of spontaneously hypertensive rats (SHR) were treated with enalapril (25-30 mg/kg per day): Group I received treatment from 4 to 14 weeks of age to inhibit development of hypertension and Group R received the drug from 14 to 20 weeks of age to reverse established hypertension. 2. Systolic blood pressure, ploidy of aortic smooth muscle cells (flow cytometric DNA analysis) and aortic hypertrophy (medial cross-sectional area) were determined at times both during and after enalapril treatment (up to 30 weeks). 3. Enalapril treatment normalized blood pressure to that of age-matched Wistar-Kyoto rats in both groups. Blood pressure rose again following cessation of treatment. 4. In untreated SHR the incidence of polyploid cells increased concomitantly with increasing pressure throughout the time studied, whereas in Group I the incidence remained low. In Group R, the incidence of polyploidy directly paralleled both the decrease (normalization) and the rise in blood pressure following cessation of treatment. 5. Hence, the incidence of vascular smooth muscle cell polyploidy is not simply a result of growth of the vessel with increasing age of the SHR, but parallels inhibition, reversal, and redevelopment of hypertension.     

VASOPRESSIN COMPENSATES FOR ACUTE LOSS OF SYMPATHETIC PRESSOR TONE IN SPONTANEOUSLY HYPERTENSIVE RATS

1. The aim of this study was to examine the pressor response of vasopressin (AVP) to an acute fall in blood pressure induced by ganglion blockade. 2. Aortic catheters were implanted in spontaneously hypertensive rats (SHR), stroke-prone SHR (SHRSP), normotensive Wistar-Kyoto (WKY), black-hooded Wistar (BHW) and Sprague-Dawley (SD) rats, aged 5–7 weeks and 7–9 months, for direct measurement of mean arterial pressure (MAP) under conscious, resting conditions. The ganglion blocking agent pentolinium was administered intra-arterially, followed by an AVP receptor antagonist specific for the pressor effect of AVP. The basal level of MAP attained with each drug was recorded. 3. In the adult SHR and SHRSP with established hypertension, acute ganglion blockade caused MAP to fall to a similar extent as in WKY, suggesting that the level of sympathetic pressor tone was similar in all three strains. Administration of the AVP antagonist alone did not affect resting MAP. During ganglion blockade, however, it caused a further reduction of MAP in WKY, SHR and SHRSP, the magnitude of which was greater in the hypertensive strains. After both drugs, the total fall in MAP and the residual MAP were significantly greater in the hypertensive rats. 4. In young rats, AVP had little effect on MAP, even during ganglion blockade. The residual level of MAP after both drugs was greater in the hypertensive strains. 5. The extent to which AVP can compensate for an acute fall in MAP increases with age and the development of hypertension. This tends to mask the loss of sympathetic mediated pressor tone after ganglion blockade. By preventing this compensation we have shown that the sympathetically mediated component of blood pressure is elevated in SHRSP with established hypertension.     

EFFECTS OF DC-015, A NOVEL POTENT AND SELECTIVE α1-ADRENOCEPTOR ANTAGONIST ON PLASMA LIPID AND VASCULAR REACTIVITY IN HYPERLIPIDAEMIC RATS

1. The effects of DC-015, a newly synthesized quinazoline derivative, on plasma lipids, lipoprotein levels and vascular reactivity were investigated in Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). 2. The hypotensive effect of DC-015 was compared with prazosin in SHR. Intravenous administration of DC-015 and prazosin (both at 0.01, 0.05 and 0.1mg/kg) induced dose-dependent reductions in mean arterial pressure (MAP) which reached a maximal effect 5 min after injection and persisted over 2 h in SHR. DC-015 decreased MAP with equal efficiency compared with prazosin. 3. The plasma levels of total cholesterol (CE), low-density lipoprotein (LDL)-CE and total triglyceride (TG) were markedly increased and the levels of high-density lipoprotein (HDL)-CE were markedly decreased in both high fat-high cholesterol (HF-HC) diet fed WKY and SHR. 4. In HF-HC diet fed WKY and SHR, the total plasma CE, LDL-CE and total plasma TG were significantly reduced after oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks. Furthermore, DC-015 therapy was associated with increased HDL-CE levels and thus the ratio of total CE to HDL-CE was improved. The antihyperlipidaemic effect of prazosin was less than that of DC-015. 5. Significantly attenuated median effective concentration (EC₅₀) values and augmented maximal responses for phenyl-ephrine-induced contraction of aortic rings were observed in HF-HC diet fed WKY and SHR. Endothelium-dependent relaxation to acetylcholine was impaired while endothelium-independent relaxation to nitroglycerin was well preserved. 6. Oral administration of DC-015 (1 mg/kg, twice a day) for 4 weeks significantly augmented EC₅₀ values and attenuated maximal responses for phenylephrine-induced contraction of aortic rings in HF-HC diet fed WKY and SHR. Prazosin (1 mg/kg, twice a day) showed a lesser extent of efficiency than DC-015 at normalization of vasorelaxation in HF-HC diet fed WKY and SHR. 7. It is concluded that DC-015, a potent antihypertensive agent, may have additional advantage in also reducing hyperlipidaemia.     

CORONARY VASCULAR RESPONSE TO ENDOTHELIN IN ISOLATED PERFUSED HEARTS OF SPONTANEOUSLY HYPERTENSIVE RATS

1. The coronary vasoconstrictive response to endothelin (ET-1) was evaluated using the isolated perfused hearts of 15 week old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY). Endothelin produced marked increases in perfusion pressure (PP) in both SHR and WKY. The effects of ET-1 were more potent than those of acetylcholine, vasopressin and angiotensin II. The vascular response to ET-1, expressed as the increase in PP, was greater in SHR than in WKY. 2. Nicardipine (10(-8) mol/L) shifted the concentration-PP response curve for ET-1 to the right. The extent of the rightward shift was greater in SHR than in WKY. Additionally in SHR, Bay K-8644 elicited a dose-dependent increase in PP, the effect being more potent than that in WKY. 3. The increased response of the coronary vasculature to ET-1 was observed after 15 weeks of age but not at 6 weeks, indicating that enhancement of the response develops with ageing in SHR. 4. Enhancement of the vascular response to ET-1 in SHR was prevented by chronic (10 weeks) treatment with enalapril (10 mg/kg per day), but not by hydralazine (30 mg/kg per day). 5. These results indicate that the coronary vascular response to ET-1 increases with age in SHR. The mechanism of the enhanced response may involve the activation of dihydropyridine-sensitive Ca2+ channels, however, this type of mechanism may also be modulated at least in part by the renin-angiotensin system.     

Chronic subcutaneous treatment with acebutolol: haemodynamic effects and metabolism in spontaneously hypertensive rats

Chronic administration of acebutolol (15 mg kg-1 s.c. three times a week for five weeks, then 30 mg kg-1 for three weeks) did not lower blood pressure in 17 and 33 weeks-old spontaneously hypertensive rats (SHR). At the end of this treatment, the plasma concentrations of acebutolol and diacetolol were measured by HPLC. After 24 h, acebutolol was absent from plasma while diacetolol was lower after chronic treatment than after acute administration. Twenty-four hours after the last injection of acebutolol, both isoprenaline-induced tachycardia and vasodilatation were reduced. The vasomotor agents, noradrenaline, bradykinin and angiotensin, exhibited the same activity in control and treated SHR. These findings suggest that the lack of antihypertensive effect of acebutolol in SHR may be the result of a decrease in diacetolol formation together with blockade of beta 2 vascular receptors.     

LONG-TERM EFFECTS OF HIGH CALORIE SUCROSE-ENRICHED DIET AND STREPTOZOTOCIN-INDUCED DIABETES ON INSULIN RESISTANCE IN SPONTANEOULY HYPERTENSIVE RATS§

1. The effects of two experimental manipulations on insulin resistance were compared in spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats. Rats were fed a high calorie sucrose-enriched diet (high calorie diet) or were made diabetic by the injection of streptozotocin (STZ). 2. After treatment with the high calorie diet for 8 weeks, blood pressure increased in SHR, but not in WKY rats. In contrast, STZ treatment decreased blood pressure in SHR, but increased it in WKY rats. 3. Plasma glucose levels during oral glucose loading were higher in SHR than in WKY rats. Glucose tolerance was impaired to a greater extent by both the high calorie diet and STZ in SHR than in WKY rats. Hyperinsulinaemia induced by the high calorie diet was severe in SHR compared with WKY rats. 4. Abnormalities in lipid metabolism induced by a high calorie diet or STZ-induced diabetes were more marked in SHR than in WKY rats. 5. Steady-state plasma glucose levels in the insulin suppression test were higher in SHR than in WKY rats, both of which were treated by either the high calorie diet or STZ. These findings indicate that insulin-stimulated glucose uptake by high calorie diet or STZ-induced diabetes was impaired to a greater extent in SHR than in WKY rats. 6. It is concluded, therefore, that SHR fed on high calorie diet or SHR with STZ-induced diabetes are suitable models to study the effects of antihypertensive treatment on glucose tolerance, insulin resistance or lipid metabolism as well as blood pressure.     

Plasma bromocriptine levels, clinical and growth hormone responses in Parkinsonism.

1. Plasma bromocriptine levels following separate oral doses of bromocriptine 12.5, 25, 50 and 100 mg have been determined in ten subjects with parkinsonism. 2. There was considerable variation between peak plasma bromocriptine levels in individual subjects after similar doses of bromocriptine. Peak levels occurred 30--210 min after dosage (mean 102 min). Peak clinical response, peak rise in plasma growth hormone level and fall in blood pressure followed shortly after peak bromocriptine levels occurred. 3. The shape of the plasma-time curve for bromocriptine was similar with all dosages. 4. There was no significant relationship between peak plasma bromocriptine levels, peak clinical response, peak increase in growth hormone and peak fall in blood pressure. However, the degree of improvement in the signs of parkinsonism was related to plasma bromocriptine levels was achieved. 5. Metoclopramide 60 mg pretreatment had no consistent effect upon plasma bromocriptine levels, the clinical or hormonal response.     

氯沙坦对自发性高血压大鼠内皮素和肾素-血管紧张素水平的对照研究

目的：动物实验观察氯沙坦的降压效果及其对血浆内皮素（ET），肾素活性和血管紧张素Ⅱ（AngⅡ)的影响。方法：24只雄性16周龄的自发性高血压大鼠（SHR）分为生理盐水（NS）组，氯沙坦（L）组和西拉普利（C）组，另用8只同龄雄性WKY大鼠对照，观察用药12周前后的血压，ET，肾素活性和AngⅡ水平。结果：与NS，C组比较，氯沙坦降压效果明显，与NS组比较，血浆ET水平在L组和C组均有明显下降，血浆肾素活性在L组明显升,AngⅡ水平，L组明显升高，而C组有所下降，结论：氯沙坦和西拉普利具有相似的降压效果。氯沙坦和西拉普利均使血管内皮细胞分泌的ET减少，西拉普利使AngⅡ水平降低，而氯沙坦使血浆AngⅡ水平升高，较高的血浆AngⅡ水平对组织器官的影响，有待进一步研究。     

The differential effects of prazosin and hydralazine on sympathoadrenal activity in conscious rats

The ability of the vasodilator hydralazine and the alpha 1-adrenoceptor antagonist prazosin to increase sympathoadrenal outflow was compared by measuring plasma norepinephrine and epinephrine concentrations, norepinephrine clearance and norepinephrine spillover rate into plasma in conscious Sprague-Dawley rats and spontaneously hypertensive rats (SHR). Even though the vasodepressor effect of 1 mg/kg (i.p.) of prazosin (-23 mm Hg) was significantly less than that caused by 1 mg/kg (i.p.) of hydralazine (-31 mm Hg) in normotensive rats, the increases in plasma norepinephrine concentration and norepinephrine spillover rate were significantly larger in prazosin-treated rats. In conscious SHR, 0.5 mg/kg (i.p.) of prazosin and 0.3 mg/kg (i.p.) of hydralazine lowered blood pressure to the same extent (-22 mm Hg), but prazosin again produced significantly larger increases in plasma norepinephrine concentration and norepinephrine spillover rate. Neither prazosin nor hydralazine affected norepinephrine clearance, and only prazosin elicited a significant rise in plasma epinephrine concentration. This differential effect of prazosin and hydralazine on sympathoadrenal activity is best explained by the differing effects of these drugs on venous return and thus the afferent activity of the cardiopulmonary baroreceptors.