The participation of brain NO synthase in blood pressure control of adult spontaneously hypertensive rats

Increased blood pressure (BP) in genetic hypertension is usually caused by high activity of sympathetic nervous system (SNS) which is enhanced by central angiotensin II but lowered by central nitric oxide (NO). We have therefore evaluated NO synthase (NOS) activity as well as neuronal NOS (nNOS), inducible NOS (iNOS) and endothelial NOS (eNOS) protein expression in brainstem and midbrain of adult spontaneously hypertensive rats (SHR) characterized by enhanced sympathetic vasoconstriction. We also studied possible participation of brain NO in antihypertensive effects of chronic captopril treatment of adult SHR. NOS activity was increased in midbrain of SHR compared to Wistar-Kyoto (WKY) rats. This could be ascribed to enhanced iNOS expression, whereas nNOS expression was unchanged and eNOS expression was reduced in this brain region. In contrast, no significant changes of NOS activity were found in brainstem of SHR in which nNOS and iNOS expression was unchanged, but eNOS expression was increased. Chronic captopril administration lowered BP of adult SHR mainly by attenuation of sympathetic tone, whereas the reduction of angiotensin II-dependent vasoconstriction and the decrease of residual BP (amelioration of structural remodeling of resistance vessels) were less important. This treatment did not affect significantly either NOS activity or expression of any NOS isoform in the two brain regions. Our data do not support the hypothesis that altered brain NO formation contributes to sympathetic hyperactivity and high BP of adult SHR with established hypertension.     

Dietary sodium restriction and blood pressure response to sympathetic blockade in young versus adolescent spontaneously hypertensive rats

The effects of dietary sodium restriction on the maintenance of blood pressure (BP) by sympathetic tone were evaluated in young versus more mature spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Sympathetic activity was assessed by BP responses to alpha 1-receptor blockade (prazosin), central inhibition of sympathetic outflow (clonidine), and by ganglionic blockade (hexamethonium). On regular sodium intake, SHR showed elevated BP and increased BP responses to sympathetic blockade at both 10 and 16 weeks of age. Sodium restriction to 9 or 17 mumols Na+/g food prevented or blunted development of hypertension in SHR when started at 4 weeks of age but did not affect BP when started at 10 weeks of age. Sodium restriction initiated in young SHR also prevented development of increased BP responses to sympathetic blockade. However, sodium restriction in more mature SHR did not decrease the increased BP responses to sympathetic blockade. We conclude that prevention of development of sympathetic hyperactivity in young SHR represents a major mechanism in the antihypertensive effect of sodium restriction in young SHR.     

Effects of salt loading and various therapies on cardiac hypertrophy and fibrosis in young spontaneously hypertensive rats

We investigated the effects of salt loading on blood pressure, cardiac hypertrophy and fibrosis as well as on the effectiveness of various antihypertensive therapies in young spontaneously hypertensive rats (SHR). Twenty-five male SHR were salt-stimulated by drinking 1% NaCl from 3 to 6 months of age. Eighteen of them were treated for the last 2 weeks of salt loading with either the angiotensin-converting enzyme inhibitor captopril, the beta-adrenergic receptor blocker propranolol or the calcium-channel antagonist verapamil. Age-matched male Wistar-Kyoto (WKY) rats and SHR drinking only water served as controls. At the age of 6 months, SHR had significantly elevated blood pressure that was unchanged by salt loading. Relative heart weight was increased in SHR without (3.3) and even more so with salt intake (3.6 vs. 2.4 in WKY). Left ventricular (LV) hypertrophy was accompanied by a 17-fold increase in the expression of mRNA for atrial natriuretic factor (ANF) both in untreated and salt-loaded SHR compared to WKY (p<0.001). Collagen I and III mRNA increased 1.7-1.8-fold in SHR without and with additional salt intake (p<0.01). None of the therapies significantly reduced blood pressure or hypertrophy. Although captopril had no antihypertensive effect, it reduced ANF, collagen I and III mRNA in LV to control level. Less pronounced effects were achieved with verapamil. These findings emphasize the cardioprotective role of captopril which may not be fully expressed in the presence of elevated salt intake.     

Blood pressure reducing effects of Phalaris canariensis in normotensive and spontaneously hypertensive rats

The birdseed Phalaris canariensis (Pc) is popularly used as an antihypertensive agent. The aqueous extract of Pc (AEPc) was administered in adult normotensive Wistar rats and spontaneously hypertensive rats (SHR) and in prehypertensive young SHR (SHR(Y), 3 weeks old). Animals received AEPc (400 mg·kg(-1)·day(-1), by gavage) for 30 days, then groups were divided into 2 subgroups: one was treated for another 30 days and the other received water instead of AEPc for 30 days. AEPc reduced systolic blood pressure (SBP) in both adult groups; however, treatment interruption was followed by a gradual return of the SBP to baseline levels. SHR(Y) became hypertensive 30 days after weaning. AEPc minimized the increase in SBP in SHR(Y), but blood pressure rose to levels similar to those in the untreated group with treatment interruption. There were no changes in renal function, diuresis, or Na(+) excretion. Pc is rich in tryptophan, and the inhibition of the metabolism of tryptophan to kynurenine, a potential vasodilator factor, prevented the blood pressure reducing effect of AEPc. Moreover, AEPc significantly reduced sympathoexcitation. Data indicate that the metabolic derivative of tryptophan, kynurenine, may be a mediator of the volume-independent antihypertensive effect of Pc, which was at least in part mediated by suppression of the sympathetic tonus.     

Insulin-exacerbated hypertension in captopril-treated spontaneously hypertensive rats: role of sympathoexcitation

Insulin excess exacerbates hypertension in spontaneously hypertensive rats (SHR). This study examined the relative contribution of the renin-angiotensin system and the sympathetic nervous system in this phenomenon. In SHR, daily subcutaneous injections of insulin were initiated either before short-term angiotensin-converting enzyme inhibition with captopril or after lifetime captopril treatment. Insulin treatment resulted in significant increases in mean arterial pressure and heart rate and captopril treatment lowered arterial pressure, but captopril did not lower arterial pressure more in the insulin-treated compared with control rats. To test the contribution of the sympathetic nervous system to this form of hypertension, each rat was intravenously infused with either a ganglionic blocker (i.e., hexamethonium) or a centrally acting alpha2-adrenergic receptor agonist (i.e., clonidine). Administration of either agent largely eliminated the differences in mean arterial pressure and heart rate between the insulin-treated and saline-treated SHR, irrespective of captopril treatment. These data indicate that in SHR, the ability of insulin to increase blood pressure is closely related to sympathoexcitation, which is unresponsive to blockade of angiotensin-converting enzyme.     

Dietary sodium intake and age in spontaneously hypertensive rats: effects on blood pressure and sympathetic activity

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 4, 7, or 10 weeks of age, and continued until 16 weeks of age. Severe sodium restriction (9 mumol/g) initiated at 2 or 4 weeks of age prevented hypertension development in SHR and severely retarded growth. Hypertension development was attenuated when 9 mumol/g was initiated at 7 weeks of age, and was not affected when started at 10 weeks of age. Mean arterial pressure (MAP) in WKY receiving 9 mumol Na/g initiated at 2 and 4 weeks of age was below normal, but was not affected when this diet was given at 7 or 10 weeks of age. Less severe sodium restriction (17 mumol Na/g) resulted in a reduction in hypertension development when initiated at 2, 4, and 7 weeks of age, but not at 10 weeks of age. MAP was normal in WKY receiving 17 mumol Na/g at all ages of diet initiation. When the 9 or 17 mumol Na/g diet were initiated at 2, 4, and 7 weeks of age, the response of blood pressure to hexamethonium administration was blunted in SHR relative to both WKY receiving the same diet, and to control SHR receiving 101 mumol Na/g. We conclude that both WKY and SHR require a minimum amount of dietary sodium for normal growth and for the achievement of normal BP in WKY, and hypertension in SHR. This sodium requirement decreases with age. SHR and WKY exhibit similar sensitivities to sodium intake with respect to body weight, but the effects on BP are more pronounced in SHR. The BP lowering effects of dietary sodium restriction may be due to a blunting of the pressor effectiveness of the sympathetic nervous system.     

Effects of aging and AT-1 receptor blockade on NO synthase expression and renal function in SHR

In an earlier study, we found increased NO production and NO synthase (NOS) expression in renal and vascular tissues of prehypertensive and adult spontaneously hypertensive rats (SHR). This study was designed to determine the effects of aging and AT-1 receptor blockade (losartan 30 mg/kg/day beginning at 8 weeks of age) on NO system in this model. Compared to the Wistar Kyoto (WKY) control rats, untreated SHR showed severe hypertension, elevated urinary NO metabolite (NO(chi)) excretion, marked upregulations of renal and vascular eNOS and iNOS proteins, normal renal function and heart weight at 9 weeks of age. Hypertension control with either AT-1 receptor or calcium channel blockade (felodipine 5 mg/kg/day) mitigated upregulation of NOS isoforms in the young SHR. With advanced age (63 weeks), the untreated SHR showed increased proteinuria, renal insufficiency, cardiomegaly, reduced urinary NO(chi) excretion and depressed renal and vascular NOS protein expressions as compared to the corresponding WKY group. AT-1 receptor blockade prevented proteinuria, renal insufficiency, cardiomegaly, and renal and vascular NOS deficiency. Thus, in young SHR, hypertension results in compensatory upregulation of renal and vascular NOS, which can be attenuated by vigorous antihypertensive therapy. With advanced age, untreated SHR exhibit cardiomegaly, renal dysfunction and marked reductions of eNOS and iNOS compared with the aged WKY rats. Hypertension control with AT-1 receptor blockade initiated early in the course of the disease prevents target organ damage and preserves renal and vascular NOS.     

Long-term effect of prazosin administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats

The sympathetic nervous system belongs to the essential systems participating in blood pressure (BP) regulation. Inhibitory intervention into the key point of its operation (alfa 1 adrenoceptors) in the prehypertensive period of spontaneously hypertensive rats (SHR) might affect the development of the hypertension in later ontogenic periods. We studied the long-term effect of prazosin administration on the cardiovascular system of young Wistar rats and SHR. Four-week-old animals were used: Wistar rats, SHR, and Wistar rats and SHR receiving prazosin (10 mg/kg/day in tap water) by gavage. Blood pressure (BP) was measured weekly by the plethysmographic method. After six weeks under anaesthesia, the carotid artery was cannulated for BP registration, and the jugular vein was cannulated for administration of drugs. Afterwards, the animals were perfused with a glutaraldehyde fixative at a pressure of 120 mmHg. The septal branch of the left descending coronary artery was processed using electron microscopy. The prazosin administration evoked the following results in both groups: a decrease of BP and heart/body weight ratio, enhancement of hypotensive responses to acetylcholine (0.1 μg, 1 μg, and 10 μg), and an increase in the inner diameter of the coronary artery without changes in wall thickness, cross sectional area (CSA) (tunica intima+media), CSA of smooth muscle cells, and extracellular matrix. In the SHR group, a reduction was observed in BP increase after noradrenaline (1 μg) application. CSA of endothelial cells which was decreased in the SHR (compared to the control Wistar rats) was increased after prazosin treatment (up to control value). Long-term prazosin administration from early ontogeny partially prevented some pathological alterations in the cardiovascular system of SHR.     

Plasma norepinephrine and dopamine-β-hydroxylase in genetic hypertensive rats

The relationship between blood pressure, plasma norepinephrine (NE), dopamine-β-hydroxylase (DBH) activity and age was investigated in spontaneously hypertensive rat (SHR), a stroke-prone substrain of the SHR and control Wistar-Kyoto rat (WKR). Blood pressure of both SHR strains increased with age and was significantly higher than that of the WKR at all ages tested (3 15 weeks). The blood pressure of stroke-prone SHR was significantly higher than that of the regular SHR after 6 weeks of age. Plasma DBH activity decreased with age in each strain, although the SHR, and especially the stroke-prone SHR, had significantly higher DBH than the controls at an early age. Plasma NE in the WKR did not change with age. Increased plasma NE was observed only in the young SHRs. The highest values were found in the 6 week old stroke-prone SHR. These data suggest that plasma DBH activity is not correlated directly with plasma NE or blood pressure, but that increased sympathetic nerve activity may occur during the development of hypertension in the SHR and the stroke-prone SHR.     

The blood pressure decrease-induced sympathetic discharge following atrial natriuretic factor administration may offset its natriuretic action

Conscious SHR and WKY rats were infused during 7 days with ANF (Arg 101-Tyr 126), 100 ng/hr/rat, by means of miniosmotic pumps and their basal blood pressure (BP), changes in sodium excretion and urinary catecholamines compared with those at the last day of the infusion. The SHR initial BP of 181 +/- 3 mmHg gradually declined to 137 +/- 5 mmHg. No significant change in blood pressure was observed in the ANF-infused WKY group. However, WKY rats exhibited an increased sodium excretion and urinary dopamine/norepinephrine ratio when compared to sham-infused rats. No such differences were observed in SHR. It is suggested that an ANF-induced withdrawal of the renal sympathetic tone permits the manifestation of its natriuretic action in WKY rats. When, however, a BP decrease predominates, as in SHR, this decrease results in a reflex sympathetic discharge with a renal sympathetic activity over-riding the ANF induced natriuresis seen in WKY rats. Secondary sympathetic responses to the ANF-induced BP decrease have to be thus taken into account when a dissociation between the hypotensive and natriuretic action of ANF is observed in vivo.     

Alterations in heme oxygenase/carbon monoxide system in pulmonary arteries in hypertension

Enhancement of the heme oxygenase/carbon monoxide (HO/CO) system has been shown to lower blood pressure (BP) in young (8 weeks), but not in adult (20 weeks) spontaneously hypertensive (SHR) rats. The reasons for this selective effect still remain puzzling. We investigated the effects of hemin on the HO/CO system of the pulmonary artery (PA) in SHR and Wistar-Kyoto (WKY) rats at different ages and evaluated the hemin-dependent changes in sGC and cGMP pathways. Hemin administration resulted in an evident reduction of BP (from 148.6 +/- 3.2 to 125.8 +/- 2.6 mmHg, P < 0.01) in young, but not in prehypertensive (4 weeks) or adult SHR or WKY rats at all ages. Coadministration of the HO inhibitor, chromium mesoporphyrin, with hemin, cancelled the BP-lowering effect of hemin. Remarkably, lower expression levels of HO-1, HO-2, and sGC paralleled with reduced HO activity and cGMP content were observed in PA from 8-week SHR rats, but not from adult SHR or WKY rats of all ages. Interestingly, hemin treatment restored these deficiencies, although the expression level of non-inducible HO-2 protein remained unchanged. We conclude that in young and prehypertensive SHR rats, an impaired HO/CO-sGC/cGMP system in the PA might be indicative of the pathogenesis and development of hypertension. In contrast, the HO/CO system in the PA of adult SHR rats was upregulated as a compensatory reaction to elevated BP and desensitization of the downstream targets of the sGC/cGMP pathway occurred.     

Cardiomyocyte volume-weighted nuclear volume and spironolactone therapy in spontaneously hypertensive rats

OBJECTIVE: To evaluate the blood pressure (BP) and cardiomyocyte nuclei hypertrophy of spontaneously hypertensive rats (SHR) treated with spironolactone and with spironolactone and an angiotensin-converting enzyme inhibitor and calcium channel blocker. STUDY DESIGN: Six groups with 5 SHR each were treated for 13 weeks: control group, spironolactone groups (5, 10 and 30 mg/kg/d, or low, moderate and high doses, respectively), and spironolactone and enlapril or/and verapamil. Blood pressure (BP) and cardiomyocyte volume-weighted nuclear volume (VWNV) were studied. RESULTS: The usual evolution of BP in young adult SHR was greatly altered by spironolactone treatment, with either attenuation or reversion of the BP tendency to increase. The treatments efficiently reduced the cardiomyocyte VWNV > 45%, confirming efficient action of both spironolactone monotherapy at moderate and high dose and spironolactone combined with enalapril or verapamil. However, the high dose of spironolactone, and spironolactone plus enalapril or verapamil showed no significant differences in cardiomyocyte VWNV. Correlation between VWNV and BP (13th week) suggested that BP degree influences cardiomyocyte VWNV. CONCLUSION: The effect of spironolactone monotherapy seems to be dose dependent, and the combination with enalapril or verapamil improves spironolactone efficiency in BP reduction but not in prevention/attenuation of cardiac myocyte nuclear hypertrophy.     

Rapid transient analysis of myosin cross-bridge kinetics in hypertrophied hearts

Essential hypertension, with pressure overload leading to left ventricular hypertrophy, often results in coronary artery disease and congestive heart failure. The spontaneously hypertensive rat (SHR) is an attractive model for studying the effects of long-term antihypertensive therapy on the contractile properties of the myocardium. In this study we investigated differences in mechanical and biochemical characteristics of papillary muscles from SHR and normal (Wistar-Kyoto [WKY]) rats as a function of age and treatment. We found that the rate of delayed force redevelopment after rapid stretch was less in SHR than in WKY in every age group studied, even at 2 wk of age, before hypertension was evident in the SHR. In the treated SHR, blood pressure was lower, hypertrophy was reduced and the rate of delayed force redevelopment was increased compared with the untreated SHR. Finally, the pattern of myosin isoenzymes was different in treated than in untreated SHR, being shifted to more of the fast V1 and less of the slow V3 isomyosin. We conclude that long-term antihypertensive therapy not only prevents the development of left ventricular hypertrophy, but may do so by preventing the shift in myosin isoenzyme pattern normally found in hearts subjected to a long-term pressure overload.     

Tissue steroid sulfatase levels, testosterone and blood pressure

The objective of this study was to examine the response of tissue steroid sulfatase (STS) levels in hypertensive rat strains, when blood pressure (BP) was lowered by different techniques at an early age. A 4×3 factoral design was used, in which males (n=6–8) from four rat strains (WKY, SHR, SHR/a, SHR/y) at 4 weeks of age, were randomly assigned to one of three treatment groups: a hydralazine group, a castration group and a control group. BP was measured by the tail cuff technique and verified by tail catheter at the end of the experiment. BP was significantly reduced by both treatments in the hypertensive strains (SHR, SHR/a, SHR/y) compared to respective control groups. At 15–17 weeks of age, animals were euthanized and heart, kidney, adrenal glands and liver were assayed for STS levels. The major trend in tissue STS was that castration significantly lowered: adrenal, heart and liver STS in specific strains. In conclusion, castration and hydralazine significantly lowered the BP in the hypertensive rat strains, but only castration consistently lowered STS levels across strains implicating testosterone as a regulator of tissue STS.     

Integrative pattern of vasomotor efficiency in SHR during ontogenesis

Numerous studies concerning the cardiovascular system in SHR often yield controversial data. The background of this diversity has various roots, ranging from different vascular segments or areas studied up to the different age of experimental animals. Our study aimed to follow the BP as an integrated response of vascular system. This approach was justified since stabilized cardiac output in SHR was proved till 1 year of age. The groups of male SHR (aged 3, 5, 9, 17 and 52 weeks) and age-matched Wistar rats were used. Significant basal BP difference between SHR and Wistar rats was found at 9 weeks of age and continued till the age of 52 weeks, reaching 189.6+/-11.9 mm Hg in SHR and 117.3+/-6.9 mm Hg in Wistar rats P<0.01 . The significant difference in BP increase to two doses of noradrenaline 0.1 microg and 1 microg between SHR and control rats was also found at the age of 9 weeks. At 52 weeks the BP increment to two doses of noradrenaline was in SHR 19.7+/-2.0 mm Hg and 60.5+/-3.9 mm Hg and in Wistar rats 7.4+/-1.9 mm Hg and 40.5+/-3.2 mm Hg P<0.01 . The hypotensive response to acetylcholine 0.1 microg, 1 microg and 10 microg in SHR was enhanced at 17 weeks of age only and this amplification persisted till the age of 52 weeks. In 52-week-old SHR the hypotensive response to three doses was 69.9+/-10.2 mm Hg, 87.5+/-11.8 mm Hg and 103.4+/-10.6 mm Hg, while in Wistar rats it was 37.4+/-4.2 mm Hg P<0.01 , 62.3+/-3.5 mm Hg P<0.01 and 73.5+/-2.8 mm Hg P<0.05 . In conclusion, the efficiency of cardiovascular system of SHR to respond to noradrenaline was already enhanced from 9 weeks of age, whereas the response to acetylcholine was not augmented before the age of 17 weeks.     

Renal cortex remodeling in streptozotocin-induced diabetic spontaneously hypertensive rats treated with olive oil, palm oil and fish oil from Menhaden

We studied the effects of edible oils intake on the renal cortical structure of streptozotocin-induced diabetic (Db) and non-diabetic spontaneously hypertensive rats (SHR). Male SHR divided into 5 groups were studied during 6 weeks: one non-diabetic SHR group and four diabetic SHR groups (three groups received by gavage olive, palm or fish oil). Kidneys were analyzed by light microscopy and stereology. Oils intake did not change the plasma glucose levels. The blood pressure (BP) was lower in SHR-Db than in SHR, but SHR-Db-fish oil showed the lowest BP. Creatinine clearance was different between diabetic SHR and non-diabetic SHR, but not between treated SHR-Db and untreated SHR-Db. The renal cortex showed scars surrounding obsolete glomeruli with inflammatory infiltrate mainly in untreated SHR-Db. The olive oil, palm oil and mainly fish oil intake retard the usual loss of glomeruli and attenuate the renal cortex adverse remodeling of Db and non-Db SHR.     

Long-term intake of edible oils benefits blood pressure and myocardial structure in spontaneously hypertensive rat (SHR) and streptozotocin diabetic SHR

The beneficial effects of edible oils long-term supplementation in blood pressure (BP) and cardiac structure were investigated in spontaneously hypertensive rat (SHR) and streptozotocin diabetic (Db) SHR (45 mg/rat i.p.). Twenty-five 12-week old male SHR were divided into four SHR-Db groups and one SHR group, SHR-Db groups each receiving, respectively, olive oil, palm oil and fish oil, and another SHR-Db group with placebo by gavage on a daily basis for 6 weeks. Myocardial structures were analyzed through light microscopy and stereology. In SHR-Db, the BP and the myocardium were significantly altered by oil supplementation. The BP, the interstitial fibrosis and cardiomyocyte size showed a significant decrease in treated SHR-Db than in SHR or untreated SHR-Db. The myocardial microvasculature and number of cardiomyocytes were higher in all treated groups, especially in fish oil group. Long-term edible oil supplementation showed beneficial effects decreasing BP levels and offsetting adverse myocardial remodeling in diabetic SHR.     

Effects of long-term treatment with captopril on the isomyosin profile of the heart from SHR and Wistar rats

Heart myosin isoforms and arterial blood pressure changes were studied in 30 SHR rats following a long-term treatment with captopril. 30 Wistar rats were included in the same trial as control. Twelve week old SHR rats with an already established hypertension and ventricular hypertrophy were orally administered with between 25 and 100 mg/Kg/die of captopril. After a ten-week treatment, animals were sacrificed and heart myosin isoforms (V1, V2, V3) analysed by polyacrylamide gel electrophoresis. Our results showed that captopril can: a) reduce blood pressure; b) reduce the cardiac hypertrophy; c) reverse the isomyosin enzymes (V1 V3) previously altered by the hypertrophy condition (V3 V1) to normal value. Furthermore we have detected an increase of V myosin isoform in SHR rats (35%) and to a lower extent in treated Wistar rats (17%). Since SHR and Wistar rats usually do not express V isoform, our results suggest that captopril may be responsible for this phenomenon by acting directly on myocardial cells.     

Effect of diabetes on aortic nitric oxide synthesis in spontaneously hypertensive rats; does captopril modulate this effect?

Nitric oxide (NO) is a potent regulator in the cardiovascular system; it is generated by the nitric oxide synthase (NOS) family of proteins. NO produced in endothelial cells plays a crucial role in vascular functions. The aim of this study was to clarify the effect of diabetes on aortic NO synthesis in a model of genetic hypertension and determine whether captopril modulates this effect. Diabetes was induced in ten weeks old spontaneously hypertensive rats (SHR) by streptozotocin injection. The rats were allocated into 3 groups: control group 1, non-diabetic SHR; group 2, diabetic SHR; group 3, diabetic SHR group receiving captopril at 80 mg/kg in drinking water for 4 weeks. Mean blood pressure (MBP) was measured once a week by tail-cuff method. Aortic NO metabolities (nitrite/nitrate) and endothelial NOS (NOS-3) were assayed by Griess reaction and by immunoblotting and immunohistochemistry, respectively. There was a significant decrease in nitrite/nitrate (NOx) in aortas of diabetic SHR compared with controls. The decrease of aortic NOx in diabetic SHR was accompanied by a decrease in NOS-3 expression. Captopril treatment reduced MBP without affecting either NOx level or NOS-3 expression in aortas of diabetic SHR. We conclude that STZ-induced diabetes decreased NO in aortas of SHR that may reflect endothelial cell dysfunction; captopril administration decreased MBP without affecting NO level in aortas of diabetic SHR which suggest that the blood pressure-lowering effects of captopril were independent of NO.     

Sympathetic-renal interaction in chronic arterial pressure control

The effects of neonatal sympathectomy of donors or recipients on posttransplantation arterial pressure were investigated in spontaneously hypertensive rats (SHR) by renal transplantation experiments. Conscious mean arterial pressure (MAP) and renal vascular resistance were 136 +/- 1 mmHg and 15.5 +/- 1.2 mmHg x ml(-1) x min x g in sympathectomized SHR (n = 8) vs. 158 +/- 4 mmHg (P < 0.001) and 20.8 +/- 1.1 mmHg x ml(-1) x min x g (P < 0.05) in controls (n = 10). Seven weeks after transplantation of a kidney from neonatally sympathectomized SHR donors, MAP in SHR recipients (n = 10) was 20 mmHg lower than in controls transplanted with a kidney from hydralazine-treated SHR (n = 10) (P < 0.05) associated with reduced sodium sensitivity of MAP. Neonatal sympathectomy also lowered MAP in F1-hybrids (F1H; SHR x Wistar-Kyoto rats). Within 6 wk after transplantation, renal grafts from untreated SHR increased MAP by 20 mmHg in sympathectomized F1H (n = 10) and by 35 mmHg in sham-treated F1H (n = 8) (P < 0.05). Neonatal sympathectomy induces chronic changes in SHR kidney function leading to a MAP reduction even when extrarenal sympathetic tone is restored. Generalized reduction in sympathetic tone resets the kidney-fluid system to reduced MAP and blunts the extent of arterial pressure rise induced by an SHR kidney graft.