BLOOD PRESSURE, PLASMA AND PITUITARY PROLACTIN RESPONSES TO BROMOCRIPTINE IN NEW ZEALAND GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

1. The effects on blood pressure (BP), plasma and pituitary prolactin (PRL) of a 13 day intraperitoneal infusion of bromocriptine (BRC) delivered by osmotic minipump were investigated in genetically hypertensive rats (GHR) and their normotensive (NT) controls. 2. In the GHR, the mean BP in the BRC-treated group over the 13 day period of study was significantly lower than in the vehicle-treated group. In the NT rats, the mean BP in the BRC-treated group over the 13 day period was also significantly lower than in the vehicle-treated group. 3. Mean plasma PRL concentration in the GHR and NT rats were comparable. In the GHR, the mean plasma PRL concentration taken on day 13 was significantly lower in the BRC-treated group than in the vehicle-treated group. In the NT rats, the mean plasma PRL concentration taken on day 13 in the BRC-treated group was, however, not significantly different from that in the vehicle-treated group. 4. The mean pituitary PRL content was not significantly different in the GH and NT rats. There was a greater suppression of pituitary PRL content in the BRC-treated GHR than in the BRC-treated NT rats compared with their respective vehicle-treated groups. 5. The results raise the possibility that PRL may have an indirect role in the pathogenesis of the hypertension of the GHR.     

INVOLVEMENT OF SYMPATHETIC NERVOUS SYSTEM INHIBITION IN THE HYPOTENSIVE EFFECT OF BROMOCRIPTINE IN SPONTANEOUSLY HYPERTENSIVE RATS

The hypotensive effect of bromocriptine in young (6 week old) spontaneously hypertensive rats (SHR) was studied. Blood pressure and plasma norepinephrine level in bromocriptine-treated SHR were significantly lower than those in vehicle-treated SHR after 3 weeks of treatment (5 mg/kg per day, i.p.), while no significant decrease of blood pressure or plasma norepinephrine level was observed after 2 weeks of treatment. These results suggest the involvement of sympathetic nervous system inhibition in the hypotensive effect of bromocriptine in SHR.     

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.     

CHANGES IN SALINE AND WATER INTAKES IN BROMOCRIPTINE-TREATED GENETICALLY HYPERTENSIVE AND NORMOTENSIVE RATS

1. We have previously reported on the effects of a 13-day intraperitoneal infusion of bromocriptine delivered by osmotic pump on blood pressure, plasma and pituitary PRL levels in genetically hypertensive (GH) rats and their normotensive (NT) controls. This paper reports further on that study in describing the changes in saline and water intakes in rats as a result of bromocriptine (BRC) treatment. 2. In the GH rats, bromocriptine did not have any significant effect on saline or water intake. 3. In the NT rats, bromocriptine significantly decreased saline intake and increased water intake. 4. The saline intake in the vehicle-treated GH rats was significantly lower than that in the vehicle-treated NT rats while the water intake was not significantly different. 5. These results indicate that differences exist between the GH and NT rats with regard to their saline and water intakes and their responses to chronic bromocriptine treatment. The changes in saline and water intakes in the GH rats seem to be different from those seen in the spontaneously hypertensive rat in another study.     

HYPOTENSIVE EFFECT OF CHRONICALLY INFUSED ADRENOMEDULLIN IN CONSCIOUS WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS

1. The hypotensive effect of chronically infused human adrenomedullin (hAM), a potent vasodilator peptide that has been reported to have a natriuretic action, was examined in normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Conscious WKY rats and SHR were infused with 200 ng/h synthetic hAM for 14 days by means of osmotic minipumps. Control groups were infused at the same schedule with 0.9% saline. Systolic blood pressure (SBP) and daily urinary excretion of Na⁺ and K⁺ were measured before and during the infusion period. In addition, plasma renin activity (PRA), aldosterone and hAM concentrations were measured on day 14 of infusion. 3. A significant reduction in SBP was observed in hAM-treated SHR at day 2 and SBP remained significantly lower throughout the experiment compared with control SHR. Similarly, SBP in the hAM-treated WKY rats was found to be significantly lower than in control WKY rats during infusion. However, the hypotensive effect was not accompanied by any significant increase in urinary volume or Na⁺ excretion in hAM-treated rats of either strain. Chronic infusion with hAM significantly suppressed PRA and lowered the concentration of plasma aldosterone in WKY rats but not in SHR. The plasma hAM levels in treated WKY rats and SHR were 0.0 ± 9.4 and 0.6 ± 0.2 fmol/mL, respectively. 4. These findings demonstrate that chronically infused hAM has a hypotensive effect in both WKY rats and SHR without an increase in urinary volume or Na⁺ excretion at a plasma AM concentration within the physiological limit.     

Delayed hypotensive effect of the thromboxane A2/prostaglandin H2 receptor antagonist S-1452 in spontaneously hypertensive rats

1. Several lines of evidence indicate that thromboxane (Tx) A2 may contribute to the development and maintenance of hypertension. The present study was undertaken to evaluate the role of TxA2 in the development of hypertension in spontaneously hypertensive rats (SHR) by using an orally active, highly specific TxA2/prostaglandin H2 receptor antagonist S-1452. 2. Vehicle (1% arabic gum solution) alone was given orally to Wistar-Kyoto (WKY) rats (n = 15) and SHR (n = 14), while S-1452 (10 mg/kg per day, twice daily) was administered orally to SHR (n = 16) for 18 weeks (from 5 to 23 weeks of age). 3. No significant difference was observed in tail-cuff blood pressure (BP) between vehicle- and S-1452-treated SHR before and at 5 and 11 weeks after treatment. Thereafter, BP was further elevated in vehicle-treated SHR, but was significantly blunted in SHR treated with S-1452 at 15 (224+/-8 vs 211+/-13 mmHg; P < 0.01) and 18 weeks (227+/-9 vs 206+/-10 mmHg; P < 0.001); this was associated with reduced proteinuria. 4. Urinary TxB2 in vehicle-treated SHR, especially during the early period, was significantly greater than that in WKY rats, while no significant difference was observed in urinary 6-ketoprostaglandin F1alpha (6-keto-PGF1alpha) between the two groups. Treatment with S-1452 reduced urinary excretion of TxB2 at 18 weeks. 5. The present study shows that S-1452, at the dose used, does not reduce BP during the early period of the development of hypertension. These results suggest that the role of enhanced TxA2 production in the development of hypertension is small, if any, in SHR. Delayed response of BP may be independent of the direct pharmacological effects of S-1452.     

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.     

Changes in plasma prekallikrein activity, blood pressure, and left ventricular thickness in hypertensive and normotensive diabetic rats

The present study examined plasma prekallikrein (PK) activity, left ventricular wall thickness (LVWT) and mean arterial blood pressure (BP) in diabetic and nondiabetic spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats. The mean arterial BP was significantly raised (p < 0.01) in diabetic WKY rats and diabetic SHR when compared with their respective controls. The LVWT was significantly (p < 0.01) increased in diabetic WKY rats when compared with that in the control WKY rats. There was also an increase (p < 0.01) in the LVWT in the SHR and diabetic SHR when compared with that in the control WKY rats and diabetic WKY rats, respectively. The plasma PK activities were higher (p < 0.01) in diabetic WKY rats, SHR, and diabetic SHR against the mean value of control WKY rats. In this animal study, these findings suggest for the first time that higher plasma PK activity may serve as an indicator for predicting high BP and left ventricular hypertrophy in diabetic and hypertensive conditions. The possible significance of these observations is discussed.     

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.     

Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: effects on substance P contents of peripheral and central nervous system tissues

The effects of s.c. capsaicin treatment on the contents of immunoreactive substance P (ISP) in several peripheral and central nervous system tissues were examined in normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Significant differences between vehicle-treated subjects of the WKY and SHR strains were observed in the ISP contents of both superior cervical and celiac sympathetic ganglia. Capsaicin pretreatment significantly reduced the ISP contents of both sympathetic ganglia in both strains. Capsaicin pretreatment significantly elevated the ISP contents of adrenal medullae only in rats of the SHR strain. The effects of s.c. capsaicin administration on the ISP contents of several selected isolated brain nuclei were also examined. No statistically significant strain or treatment differences in the SIP contents of the nucleus tractus solitarii nucleus locus ceruleus and periaqueductal central gray were observed. The ISP contents of the nucleus raphe magnus, periventricular preoptic area, and nucleus amygdaloideus medialis were significantly greater in vehicle-treated SHR rats than in vehicle-treated WKY animals. Capsaicin pretreatment significantly increased the ISP contents of both the periventricular preoptic area and nucleus amygdaloideus medialis in SHR rats. These results indicate that the effects of capsaicin treatment of the ISP contents of nervous systems tissues vary with both the tissues examined and the strain of rat. In addition, the previously reported long-lasting hypotensive effect produced by capsaicin in both the WKY and SHR strains may be related to the significant depletion of the ISP contents in peripheral sympathetic ganglia in both strains.     

Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats

1. The effects of an oral daily dose (10 mg kg(-1)) of the flavonoid quercetin for 5 weeks in spontaneously hypertensive (SHR) and normotensive Wistar Kyoto rats (WKY) were analysed. 2. Quercetin induced a significant reduction in systolic (-18%), diastolic (-23%) and mean (-21%) arterial blood pressure and heart rate (-12%) in SHR but not in WKY rats. 3. The left ventricular weight index and the kidney weight index in vehicle-treated SHR were significantly greater than in control WKY and these parameters were significantly reduced in quercetin-treated SHR in parallel with the reduction in systolic blood pressure. 4. Quercetin had no effect on the vasodilator responses to sodium nitroprusside or to the vasoconstrictor responses to noradrenaline or KCl but enhanced the endothelium-dependent relaxation to acetylcholine (E(max)=58+/-5% vs 78+/-5%, P<0.01) in isolated aortae. 5. The 24 h urinary isoprostane F(2 alpha) excretion and the plasma malonyldialdehyde (MDA) levels in SHR rats were increased as compared to WKY rats. However, in quercetin-treated SHR rats both parameters were similar to those of vehicle-treated WKY. 6. These data demonstrate that quercetin reduces the elevated blood pressure, the cardiac and renal hypertrophy and the functional vascular changes in SHR rats without effect on WKY. These effects were associated with a reduced oxidant status due to the antioxidant properties of the drug.     

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.     

Age-dependent hyperresponsiveness of spontaneously hypertensive rats to the pressor effects of intravenous neuropeptide Y (NPY): role of mode of peptide administration and plasma NPY-like immunoreactivity.

The effects of various doses of intravenously (i.v.) infused (5-min duration, 0.1-3.2 nmol/kg/min) or bolus-injected (0.1-3.2 nmol/kg) porcine and/or rat/human neuropeptide Y (NPY) on mean arterial pressure (MAP), heart rate (HR), and plasma concentrations of porcine NPY-like immunoreactivity (pNPYir) were examined in conscious, unrestrained spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats of various ages. When administered as an infusion to 12- to 17-week-old SHR, WKY, and SD rats, porcine NPY (pNPY) was more potent in increasing MAP in SHR than in either WKY or SD rats. Infusions of rat/human NPY instead of pNPY resulted in similar increases in potency in 12- to 17-week-old SHR as compared with WKY. This potency-associated hyperresponsiveness to infused pNPY was also observed when 36- to 41-week-old and 6-week-old SHR and WKY were examined, but infused NPY induced similar HR reductions in age-matched rats regardless of rat strain. Furthermore, doses of infused pNPY that elicited significantly greater pressor responses in SHR and WKY (0.32 nmol/kg/min in 12- to 17-week-old rats and 1.0 nmol/kg/min in 6-week-old rats) resulted in essentially identical plasma pNPYir concentrations in the two rat strains. In contrast, hyperresponsiveness to the MAP effects of bolus injections of pNPY in 12- to 17-week-old SHR was manifested as an increase in efficacy rather than potency, was associated with significantly smaller reductions in HR in SHR than in WKY and occurred at plasma pNPYir concentrations that were significantly larger than those required for infusion-associated hyperresponsiveness. These results are consistent with the hypothesis that NPY is an important contributor to the development and maintenance of essential hypertension.     

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.     

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.     

Gender differences in blood pressure and heart rate in spontaneously hypertensive and Wistar-Kyoto rats

1. In general, premenopausal women are known to have lower blood pressure than men and animal models have shown a similar sexual dimorphism. However, many studies in animals have been performed using anaesthetized or restrained models. Current experiments were conducted to investigate the relationships among resting heart rate, blood pressure and gender in conscious, unrestrained normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). 2. Biotelemetry transmitters were implanted in 6-month-old animals. Values for heart rate, diastolic blood pressure, systolic blood pressure and pulse pressure were recorded continuously at 10 min intervals after all animals recovered completely from surgery. 3. Normal circadian rhythms in heart rate were found in all rats, with no significant differences among the four groups; the circadian variation in blood pressure was evident in all groups, although much smaller. Heart rate was found to be higher in WKY female rats than in the other three groups. Male WKY rats, male SHR and female SHR had similar heart rates. Male SHR had significantly higher systolic and diastolic blood pressures than female SHR. Male and female WKY rats had similar diastolic blood pressure, but males had slightly higher systolic pressure than females. No significant difference in pulse pressure was found in WKY male and female rats. Male SHR showed significantly higher pulse pressure than female SHR at most times during the day. 4. In conclusion, these results indicate that hypertension is exacerbated in male SHR compared with females under conscious resting conditions and demonstrate that the higher heart rate observed in WKY female rats is not present in the SHR model.     

Atrial natriuretic factor and volume expansion-induced natriuresis in the spontaneously hypertensive rat.

The implication of atrial natriuretic factor (ANF) during acute volume expansion in the spontaneously hypertensive rat (SHR) was evaluated. The effect of short-term afterload relief was also investigated. Fourteen- to 15-week-old SHR and Wistar-Kyoto (WKY) rats were treated with hydralazine for 5 days. The systolic blood pressure (BP) of SHR decreased to normotensive levels but cardiac hypertrophy was not reduced. Isotonic, iso-oncotic volume expansion (equivalent to 10% of total blood volume) was performed 3 times at 15-min intervals on conscious animals. The effect of volume expansion on central venous pressure was identical among the groups. Changes in left ventricular end-diastolic pressure (LVEDP) induced by volume expansion were greater in SHR than in WKY rats and were not affected by treatment. The increases in plasma N-terminal ANF (ANF-(1-98)) concentrations were larger in both treated and untreated SHR verses WKY rats. Despite enhanced ANF release in SHR, the overall magnitude of the diuretic and natriuretic responses to volume expansion was similar in all groups. The natriuretic response was strongly correlated with plasma ANF in WKY rats, this relationship was weak in control SHR, and restored by treatment. It is suggested that ANF release is not impaired in SHR at a 10% volume load; however, there seems to be a lower renal responsiveness to ANF in SHR.     

Down-regulation of brain and spinal cord K-opiate receptors in spontaneously hypertensive, Wistar-Kyoto normotensive, and Sprague-Dawley rats by chronic treatment with U-50, 488H.

The effects of chronic administration of U-50,488H, a K-opiate receptor agonist, on the binding of [3H]ethylketocyclazocine ([3H]EKC) to K-opiate receptors on the cerebral cortical and spinal cord membranes of spontaneously hypertensive (SHR), Wistar-Kyoto normotensive (WKY), and Sprague-Dawley (SD) rats were determined. Age-matched (10 weeks old) male rats of each strain were injected twice daily for 7 days with either U-50,488H (25 mg/kg, i.p.) or its vehicle. On day 8, the rats were killed. The cerebral cortex and the spinal cord were isolated for binding studies. The systolic blood pressure and heart rate of SD and WKY rats did not differ but the blood pressure of SHR rats were higher than that of SD and WKY rats. The receptor density (Bmax) and apparent dissociation constant (Kd) values of [3H]EKC binding to the spinal cord of WKY and SHR rats did not differ. However, the spinal cord of SD rats had higher Bmax and Kd values than WKY or SHR rats. The cortex of the SD rats had a lower Bmax value than the other two strains. Treatment with U-50,488H decreased the Bmax value of [3H]EKC in spinal cord of SD rats, increased the Kd value in SHR rats, and had no effect in WKY rats. Decreases in the Bmax value were produced in the cortex of all strains of rats, but a greater effect was observed in WKY and SHR rats than in SD rats.     

DIFFERENTIAL REGULATION OF UTERINE AND GLOMERULAR ANGIOTENSIN II RECEPTORS IN NORMAL AND HYPERTENSIVE PREGNANCY IN THE RAT

1. In the non-pregnant state uterine and glomerular angiotensin II (AII) receptors have been shown to regulate in a similar fashion. This study sought to determine whether such parallel regulation occurred during pregnancy. We also investigated the role of plasma AII in these changes. 2. These studies were performed in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The SHR has increased receptor number, increased sensitivity to infused AII and decreased plasma volume compared to the WKY. These features are also seen in pregnancy induced hypertension (PIH). 3. Age matched female WKY and SHR were exposed to an appropriate breeder and sacrificed on day 14 of gestation. Plasma AII was measured by radio-immunoassay. Uterine and glomerular receptor binding was determined by saturation analysis using ¹²⁵I(Sar¹,Ileu⁸)AII. Data were analysed using the program ligand. 4. Uterine and glomerular AII receptors showed different patterns of regulation during pregnancy. The uterine AII receptor affinity decreased significantly in both strains at 14 days of gestation and receptor number also decreased significantly in WKY. In contrast, glomerular AII receptor affinity did not change significantly in either strain. Receptor numbers in the glomeruli increased significantly compared to their respective non-pregnant controls. 5. We conclude that the uterine and glomerular AII receptors do not regulate in a parallel fashion in pregnancy. Plasma AII concentration does not appear to be involved in the regulation of either uterine and glomerular receptor expression in pregnancy.     

Differences in kidney renin content between normotensive and spontaneously hypertensive rats: effect of captopril treatment

Kidney renin concentrations were significantly lower in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto (WKY) rats. After treatment of both SHR and WKY rats with captopril (100 mg/kg p.o. for 3 months), kidney renin concentration increased dramatically in SHR and slightly, but significantly, in WKY. After captopril treatment, kidney renin content of SHR was still significantly lower than WKY. Because of the lower content of kidney renin in SHR and the proportionately greater increase in kidney renin content in SHR after captopril treatment than in WKY, it is proposed that a fundamental difference(s) in the control of the renin-angiotensin system exists in SHR, an effect which may or may not be related to SHR hypertension.