Development Of Renovascular Hypertension Research Articles

Ebelactone B, an Inhibitor of Extracellular Cathepsin A-Type Enzyme, Suppresses Platelet Aggregation Ex Vivo in Renovascular Hypertensive Rats

The present study was undertaken to investigate whether ebelactone B, an inhibitor of bradykinin and angiotensin I hydrolysis by serine carboxypeptidase Y-like enzymes, could influence platelet aggregation ex vivo in renovascular hypertensive rats (2-kidney, 1-clip Goldblatt model, 2K1C). We found that ebelactone B (5 mg/kg) administrated subcutaneously once a day for 5 days, 5 weeks after the development of hypertension, or a single dose of ebelactone B (0.5 mg/kg) injected intravenously into 2K1C hypertensive rats before the induction of arterial thrombosis, both markedly suppressed collagen-induced platelet aggregation in whole blood. In contrast, inhibition of collagen-induced platelet aggregation was not evident in vitro after pretreatment of the blood with ebelactone B, indicating that ex vivo the antiaggregatory action of this compound can proceed through an indirect mechanism. The injection of ebelactone B did not affect the mean blood pressure of 2K1C hypertensive rats but lowered an elevated extracellular serine carboxypeptidase cathepsin A-like activity. Thus, the data indicate that ebelactone B may be a promising antiaggregatory agent in renovascular hypertension and suggest that 1 of the possible mechanisms through which it exerts this effect may be related to the suppression of cathepsin A-like activity released locally during the development of renovascular hypertension.

Alteration of local ACE activity and vascular responsiveness during development of 2K1C renovascular hypertension

Objectives: This study sought to examine the correlation between development of hypertension and local, including; aorta, heart, kidney, lung, as well as circulatory (serum) ACE activity in two kidney one clip (2K1C) renovascular hypertension. Methods: Ten- to twelve-week-old rats undertaken left renal artery clipping. Experiments were carried out in 2, 4, 8, and 12 weeks after induction of hypertension (2, 4, 8 and 12W). After sacrificing, animals blood and tissues including heart, aorta lung and kidney were dissected out and homogenized in Trizma buffer. ACE activity was determined by hydrolysis of the synthetic substrate, Hip-His-Leu and the amount of hippuric acid liberated from the substrate were analyzed by HPLC. Vascular responsiveness was measured using perfusion pressure method. Results: The systolic blood pressure (SBP) was gradually increased in 2K1C animals and was markedly higher compared to that of controls. The ACE activity in all tissues from 2K1C was significantly different in all groups of 2, 4, 8, and 12 weeks after surgery. The serum ACE activity of 2K1C was markedly increased in 2 and 4W and reached to plateau in 8 and 12W group. Vascular resposiveness to angiotensin I (AngI) was increased during development of hypertension in all groups of animals. Conclusion: These results indicated that there is a positive correlation between augmentation of blood pressure and local ACE activity in various tissues as well as serum, highlighting the significant contribution of local compared to circulatory ACE activity in development of renovascular hypertension.

Angiotensin I-converting enzyme gene polymorphism influences chronic hypertensive response in the rat Goldblatt model

In humans, the insertion/deletion polymorphism in the angiotensin (Ang) I converting enzyme (ACE) gene significantly determines ACE activity. The deletion allele induces higher ACE levels and is associated with hypertension in men. In the rat, a microsatellite marker in the ACE gene allows differentiation of the ACE alleles among strains with different ACE levels. We evaluated the effect of genetically determined ACE expression on the development of renovascular hypertension in the rat. Systolic BP (SBP), ACE and angiotensin II (Ang II) levels were measured using the Goldblatt (Gb) model (two kidneys, one clip) in homozygous males of two inbred strains (F2) of Lewis x Brown-Norway (BN) rats. SBP was significantly higher in the BN-Gb rats compared to the Lewis-Gb rats throughout the study (F = 239.6, P < 0.001). An interaction was observed between SBP and strain (F = 2.92, P < 0.01). Plasma ACE activity was 100% higher in the BN-Gb than in the Lewis-Gb rats (P < 0.05). Ang II plasma levels were higher in the BN-sham than in the Lewis-sham rats (255 +/- 22 versus 161 +/- 16 pg/ml, P < 0.05), increased in both Gb groups and correlated significantly with SBP (r = 0.58, P < 0.01). Genetically determined ACE expression in male rats enhances the chronic hypertensive response after the induction of renovascular hypertension. A relationship between circulating Ang II and the development of hypertension was also observed in this experimental model of genetically modulated hypertension.

Endovascular revascularization of renal artery stenosis: Technical and clinical results

Purpose: The natural history of renal artery stenosis is progression with subsequent deterioration of kidney function and development of renovascular hypertension. Percutaneous transluminal renal angioplasty is effective in the treatment of nonostial lesions but less effective for ostial stenoses. Because of the poor technical success experienced with percutaneous transluminal renal angioplasty, stenting of ostial stenoses is becoming the standard of endovascular care. In this retrospective study we analyzed the technical and clinical outcomes after renal artery stenting in 73 consecutive patients. Patients and Methods: From July 1992 to January 1999, 88 Palmaz stents were deployed in 85 renal artery stenoses in 73 patients, with a mean age of 67.9 ± 9.4 years. Twelve patients (16%) underwent bilateral stent placement. Atheromatous lesions were the most prevalent (99%: 82% ostial, 16% nonostial). Most stents were implanted for suboptimal balloon dilation (52%) or dissection (24%). Mean percent stenosis was 86% ± 12%. Renal insufficiency (creatinine level ≥ 1.5 mg/dL) was present in 50 (68%) patients, and uncontrolled hypertension (systolic ≥ 160 mm Hg or diastolic ≥ 90 mm Hg with more than two medications) was present in 57 (78%). Results: Primary technical success was achieved in 89%. At the initial procedure, three additional stents were placed for residual stenoses, and urokinase was used to treat one intraprocedural stent thrombosis, resulting in an assisted primary technical success rate of 94%. Major complications occurred in 9.1% of stents placed: access artery thrombosis (n = 4), renal artery extravasation (n = 1), renal artery thrombosis (n = 1), and hematoma requiring operation (n = 2). Long-term clinical data were available on 69 (95%) patients at 20 ± 17 months. Overall, a significant decrease in systolic and diastolic pressures (P <.001) and reduction of medication (P <.01) were noted without a change in renal function (P = NS). Angiography was performed on 22 patients at 11.3 ± 10.3 months for persistent or worsening renal function or hypertension or for other reasons; 10 patients had significant restenoses in 14 renal arteries. Conclusion: Our retrospective analysis demonstrates that endovascular stenting of renal artery stenosis in patients with poorly controlled hypertension or deteriorating renal function is a safe and effective alternative treatment to surgical management. (J Vasc Surg 2001;33:1041-9.)

Dietary n-3 polyunsaturated fatty acids affect the development of renovascular hypertension in rats.

The consequences of a dietary n-3 PUFA supply was investigated on the blood pressure (BP) increase elicited by left renal artery stenosis in rats distributed in 3 groups (n = 8) fed for 8 weeks a semi-purified diet either as control diet or enriched diets (docosahexaenoic acid, DHA, or eicosapentaenoic acid, EPA). The PUFA intake induced large alterations in heart and kidney phospholipid fatty acid profile, but did not influence body weight, cardiac hypertrophy, renal left atrophy and right hypertrophy. Within 4 weeks, BP raised from 120-180 +/- 2 mm Hg in the control group, but only to 165 +/- 3 mm Hg in the n-3 PUFA groups. After stabilization of BP in the 3 groups, the rats received a short administration of increasing dose of perindopril. The lower dose (0.5 mg/kg) moderately decreased BP only in the control group. With higher doses (1, 5 and 10 mg/kg) BP was normalized in the 3 groups, with a higher amplitude of the BP lowering effect in the control group. A moderate n-3 PUFA intake can contribute to prevent the development of peripheral hypertension in rats by a mechanism that may involve angiotensin converting enzyme.

Expression of angiotensin-converting enzyme in renovascular hypertensive rat kidney.

We hypothesized that the gene expression of angiotensinogen, angiotensin-converting enzyme, and angiotensin II type 1 receptor, in addition to renin, is increased in kidneys after renal artery stenosis. Two-kidney, one clip renovascular hypertension was initiated in Sprague-Dawley rats by clipping of the left renal artery; control rats were sham operated. Blood pressure was not changed for the first 2 days after clipping but was elevated on day 4 (mean arterial pressure, 104 +/- 4 versus 87 +/- 2 mm Hg in sham-operated control rats, P < .002) and increased further during the next 24 days. Rats were killed 2, 4, 7, 14, and 28 days after clipping or sham operation, and poly(A)(+)-purified renal cortical RNA was analyzed by Northern blotting. Autoradiographs were quantitated by densitometry and normalized for the expression of a housekeeping gene. Renin expression was increased in the clipped kidney (by 149% on day 2) and decreased in the nonclipped kidney (by 82% on day 2), compared with kidneys of control rats. Expression of the angiotensin-converting enzyme was increased in clipped kidneys from the first day after clipping (158%) and throughout the experiment (66% on day 28), but was unchanged or slightly decreased in nonclipped kidneys. Angiotensinogen mRNA showed little change. Angiotensin II type 1 receptor expression was decreased in nonclipped kidneys but unchanged during the first 7 days in clipped kidneys. Our results show that components of the renin-angiotensin system other than renin are also differentially expressed in clipped kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)

Time course of cardiac sympathetic and vagal tone changes in renovascular hypertensive rats.

The present study has examined the time course of autonomic tone changes in two-kidney, one-clip (2K1C) and one-kidney, one-clip (1K1C) renal hypertension. In conscious rats, cardiac sympathetic and vagal tone were determined using propranolol and atropine, respectively. The development of renovascular hypertension was accompanied by a significant tachycardia, increase in cardiac sympathetic tone and decrease in cardiac vagal tone. In the isolated perfused heart we observed a reduced chronotropic response to isoproterenol. These alterations were transitory in 2K1C and greater and more persistent in 1K1C renal hypertension. These results show the relative role played by the cardiac sympathetic and vagal systems in the maintenance of tachycardia in renovascular hypertension.

Renal nerve activity does not contribute to the development of renovascular hypertension in rats with abdominal aortic constriction

This study examines the influence of renal nerves on the development of renovascular hypertension in proximal aortic constricted rats. The rats were studied 1 week after unilateral or bilateral denervation of the renal artery. Denervation had no effect on the increase in mean arterial pressure induced by the constriction. The glomerular filtration rate and filtration fraction in control and in proximal aortic constricted rats were not influenced by the denervation. The Na excretion was increased in the denervated kidney both in control and in proximal aortic constricted rats. Plasma angiotensin II levels were not different from controls in innervated or unilaterally denervated proximal aortic constricted rats. In bilaterally denervated proximal aortic constricted rats the plasma angiotensin II levels were significantly higher. The renovascular hypertension and the alteration in renal function in proximal aortic constricted rats are not dependent on renal nerve activity.

Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats

To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS)

Development of renovascular hypertension after central serotonin depletion.

The participation of the central serotonergic system in the development of two-kidney, two clip (2K2C) Goldblatt renovascular hypertension in the rat has been examined. Half of the rats were treated with desmethylimipramine intraperitoneally and 5,7-dihydroxytryptamine intracisternally; the other half received only desmethylimipramine and the 5,7-dihydroxytryptamine vehicle. Two days later, a silver clip was placed in both renal arteries in half of the rats of each group. A sham operation was performed in the remaining rats. Blood pressure was recorded during the 5 weeks after treatment. At the end of the experiment, blood and cerebrospinal fluid samples were obtained. The brain was dissected into several areas and kept frozen. Norepinephrine, serotonin, angiotensinogen, and renin-like concentration were evaluated in the brain areas. Plasma renin activity and angiotensinogen concentration in the plasma and cerebrospinal fluid were estimated. In the sham-operated groups, blood pressure was lower in the treated than in the control rats. The curve of blood pressure increase, as well as the final blood pressure, was similar in the treated and control 2K2C rats. Serotonin was significantly depleted by the 5,7-dihydroxytryptamine treatment in all brain areas. Treatment did not induce any changes in central norepinephrine concentration. Plasma renin activity was diminished in the treated sham-operated rats. These data indicate that the central serotonin depletion does not prevent the development of hypertension and confirm the role of the amine in normal blood pressure regulation. On the other hand, the peripheral renin-angiotensin system might participate in the development of high blood pressure in serotonin-depleted animals.

Stimulation of plasma renin activity by captopril in renovascular hypertensive conscious dogs.

The increase in plasma renin activity induced by captopril is used in the clinical evaluation of renovascular hypertensive patients. This increase in plasma renin activity could result from either the concomitant fall in systemic pressure or other effects of captopril, such as the removal of an angiotensin II inhibitory effect on renin release, the increased production of bradykinin or prostaglandins, etc. To examine the effect captopril has on plasma renin activity, independent of changes in systemic pressure, captopril (5, 10 and 50 micrograms/kg iv) was administered to conscious dogs before and following the development of 1 clip-2 kidney Goldblatt hypertension. Plasma renin activity, under normal conditions remained unchanged, while during hypertension it increased 2.0, 2.8 and 3.5 fold respectively in response to the three doses of captopril. These results suggest that the development of renovascular hypertension sensitized the kidney to release renin when challenged by captopril and that the effect is independent of changes in systemic pressure.

Naloxone attenuates development of hypertension in two-kidney one-clip Goldblatt rats.

The present experiments were designed to determine if an opiate antagonist affects blood pressure in two-kidney one-clip Goldblatt rats. Male Sprague-Dawley rats were divided into three groups. Group 1 received an infusion of saline intraperitoneally via an osmotic pump and left renal artery constriction (RAC). In group 2, rats were treated the same as group 1, except that they received an intraperitoneal infusion of naloxone (100 micrograms/h). Group 3 received the same infusion of naloxone without RAC. Naloxone-infused Goldblatt rats showed a significantly lower systolic blood pressure (SBP) than saline-infused Goldblatt rats (132 +/- 7 vs. 160 +/- 9 mmHg at day 14), but a higher SBP than control (132 +/- 7 vs. 106 +/- 1 mmHg). Infusion of naloxone did not significantly change SBP in normotensive rats. Renal renin activity in the clipped kidney was higher than in the nonclipped kidney in groups 1 and 2. Plasma renin activity (PRA) in both groups of Goldblatt rats was higher than in group 3, but no significant difference was found between the two groups of Goldblatt rats (groups 1 and 2). Naloxone (1.5 microM) did not affect the basal secretion of renin by isolated cortical slices from untreated rats. The present data demonstrate that naloxone significantly attenuates the development of hypertension in two-kidney one-clip rats. The attenuation of blood pressure was not associated with the changes in PRA, renal renin activity, or plasma aldosterone concentrations. The data support the hypothesis that the endogenous opioid system may be involved in the development of renovascular hypertension.

In vivo arteriolar reactivity to norepinephrine and calcium in one-kidney, one-clip Goldblatt hypertensive rats.

The in vivo reactivity of small arterioles to norepinephrine and to changes in external calcium was investigated in normotensive (NT) and one-kidney, one-clip Goldblatt hypertensive rats (1K1C). Rats were anesthetized with sodium pentobarbital (50 mg/kg) and arterioles in the cremaster muscle were exposed to increasing concentrations of either norepinephrine (10(-10) to 10(-5) M) or of bath calcium (0 to 5.1 mM). Third-order arterioles of 1K1C showed almost a ten-fold increased reactivity to NE compared to arterioles of NT rats (pD2 values of 7.88 +/- .43 vs 6.92 +/- .30). Arterioles of 1K1C rats showed an increased reactivity to re-exposure to calcium (0.65 to 5.10 mM). Following exposure to phentolamine this hyper-reactivity was abolished and arterioles of 1K1C and NT exhibited similar responses to changes in bath calcium concentrations, suggesting that the increased reactivity in the 1K1C was due to stimulation of endogenous norepinephrine release. When arterioles were exposed to increasing bath concentrations of the calcium entry blockers, verapamil and diltiazem, dilator responses were similar for 1K1C and NT groups. Collectively, these data suggest that during the development of renovascular hypertension, observed increases in arteriolar reactivity involve an increase in the receptor mediated entry of extracellular calcium into vascular smooth muscle and no change in non-receptor-mediated entry of calcium.

Suppression of renin release by antagonism of endogenous opiates in the dog.

The influence of blockade of endogenous opioids on the release of renin due to partial renal arterial constriction was determined acutely and chronically in unilaterally nephrectomized dogs. In acute preparations changes in plasma renin activity, arterial blood pressure, and heart rate were determined after 15 min of 60% renal arterial constriction before and after administration of either a saline vehicle, the opiate antagonist naloxone (0.05 mg/kg), or morphine (2 mg/kg). Acute antagonism of endogenous opiates abolished the increase in plasma renin activity and mean arterial pressure associated with renal arterial constriction. Repeated renal arterial constrictions in saline- or morphine-treated animals did not alter the humoral or hemodynamic responses. In chronic preparations long-term naloxone infusion attenuated the development of renovascular hypertension and diminished the increase in plasma renin activity. These data suggest that endogenous opioid peptides are modulators in the control of renin release and may be important participants in the pathogenesis of hypertension.

Enzyme-histochemical study of function of the medulla oblongata in rats with renovascular hypertension

Renovascular hypertension (RVH) is one of the most widely used models of arterial hypertension [3]. It is traditionally considered that the blood pressure (BP) rises under these conditions as a result of the action of humoral factors (angiotensin or sodium) on peripheral vascular tone [9]. However, we know that central desympathization or destruction in the anterior hypothalamus can prevent the development of RVH [6, 7], evidence that central mechanisms also are involved in the pathogenesis of the disease. An important role in the central regulation of the circulation is played by structures of the medulla oblongata [I, 2, 5]. One way of assessing function of different parts of the brain is to study the intensity of their energy metabolism. Investigations by autoradiography with labeled deoxyglucose have shown that the development of spontaneous hypertension in rats, and also acute fluctuations of BP, are accompanied by changes in metabolic activity of several structures of the medulla [ii, 14]o No experiments of this kind have been conducted on animals with RVH.

Progressive microvascular alterations with the development of renovascular hypertension.

Norepinephrine-induced changes in diameters of first- (1A), second- (2A), and third-order (3A) arterioles in the exposed cremaster muscles of normotensive and renovascular hypertensive rats were quantitated via television microscopy. By 2 weeks following the surgery to induce hypertension, we found that 3A sensitivity to norepinephrine had increased and the 1As had chronically constricted. By 4 weeks, the constriction had progressed to include both 1A and 2A. Sensitivity was no longer increased in 3As and, in fact, sensitivity had decreased in 1As and 2As. The 1As and 2As could not be dilated with isoproterenol or nitroprusside; thus, the vessels appeared to have undergone a structural alteration. We suggest from these results that the early increased 3A sensitivity contributes to the initial development of hypertension. The larger arterioles then constrict to protect the downstream vessels from increased luminal pressure. As the hypertension develops, the constriction progresses to smaller arterioles in an attempt to maintain normal pressure in the capillaries (site of water exchange). The constricted arterioles contribute to increased total peripheral resistance, and with the constriction, there occurs a general decrease in vessel responsiveness.

The compression syndrome of the left renal vein (author's transl)

Severe compression of the left renal vein produces a pressure gradient between it and the inferior vena cava and results in changes in haemodynamics. The cause of the narrowing is usually the aorta, less commonly the superior mesenteric artery. Compression of the left renal vein may be responsible for a number of abnormalities such as primary varicoceles, primary varices of the ovarian, renal, pelvic and ureteric veins on the left, the more frequent occurrence of unilateral renal vein thrombosis on the left and the development of renovascular hypertension. One hundred and twenty-three selective phlebograms of the left renal vein and CT examinations of this structure in a further 87 patients acting as a control group were carried out. The significance of compression of the left renal vein as an aetiological factor in the development of the above mentioned abnormalities is discussed.

Angiotensin I converting enzyme activity in portal vein studied in normotensive rats and in models of primary and secondary hypertension.

The effects of angiotensin I (AT I), angiotensin II (AT II) and the activity of AT I converting enzyme (ACE) were investigated in isolated portal veins of normotensive rats (WKR and NCR) and of rats with primary (SHR) and secondary (one clip 2 kidney renal; RHR) hypertension. Based on ED50 values, the tissue sensitivity to AT II was slightly less in the portal veins of RHR than SHR, while the sensitivity of smooth muscle in NCR and WKR was similar to that of SHR. Angiotensin I induced contractions were inhibited by saralasin and by captopril, indicating presence of functionally active converting enzyme in the this vascular tissue. The local concentration of AT II formed from AT I, was evaluated based on AT II dose response curves and AT I response magnitude. The AT II formation was essentially similar in SHR, WKR and NCR and slightly enhanced in RHR. Inhibition of AT II formation with captopril and/or blockade of AT II receptors with saralasin failed to alter the spontaneous myogenic activity of the portal vein. Captopril reduced smooth muscle activity only in concentration several orders of magnitude greater than that needed to inhibit ACE. The concentration of captopril needed to inhibit AT I responses was similar in all strains of rats. It is concluded that AT II is rapidly formed in the portal vein due to local conversion of AT I. In the RHR portal vein the extent of AT I conversion is increased and the tissue sensitivity to AT II is decreased possibly due to mechanisms involved in the development of renovascular hypertension.

Baroreflex Sensitivity Changes during the Development of Goldblatt Two-Kidney One-Clip Hypertension in Rats

1. The time course of changes in baroreceptor reflex sensitivity during the development of renovascular hypertension was studied in male Wistar rats in which the left renal arteries were constricted by silver wire clips of 0.18 mm internal diameter. 2. Groups of animals were studied at 3, 7, 14 and 25 days after induction of renovascular hypertension. Rats of comparable ages were included as controls. There was a significant decrease in mean baroreflex sensitivity from 0.950 +/- 0.157 ms/mmHg (n = 8) in the normal control group to 0.537 +/- 0.105 ms/mmHg (n = 8) in the 3 day hypertensive group (P < 0.05). Baroreflex sensitivity in the 3 day hypertensive rats was independent of the level of arterial pressure achieved in individual animals. 3. These changes in baroreflex sensitivity at 3 days precede the development of left ventricular hypertrophy and, as previously shown in this model, also precede structural vascular adaptation and resetting of the carotid sinus baroreceptor threshold. 4. A further loss of baroreflex sensitivity, which may be structurally based, occurred later. Baroreflex sensitivity in the 14 day hypertensive rats fell to 0.182 +/- 0.039 ms/mmHg (n = 8) compared with the 3 day hypertensive rats (P < 0.01).

Increased hypothalamic noradrenergic activity in one-kidney, one-clip renovascular hypertensive rats.

To further define central and peripheral sympathetic nerve activity in the one-kidney and two-kidney, one-clip models of renovascular hypertension, plasma catecholamines and regional brain norepinephrine of these models were compared with the activities of their brain biosynthetic enzymes: tyrosine hydroxylase (TYH) and dopamine-beta-hydroxylase (DBH). Findings in the groups of 20 one-kidney and 17 two-kidney female Wistar rats were compared with those in 10 sham-operated rats. Systolic blood pressure, measured indirectly, and the mean arterial pressure, measured directly from the femoral arteries, verified development of renovascular hypertension in both the one and two-kidney animals. Plasma norepinephrine increased from 248 +/- 46 to 401 +/- 66 pg/ml in the one-kidney group only (p < 0.001). Hypothalamic TYH and DBH activities of the one-kidney animals were 48 and 34% greater than those of the two-kidney animals and 28 and 39% greater than the sham-operated animals. The multiple t-test indicated significant differences between the mean hypothalamic THY of the one- and two-kidney groups and between the hypothalamic DBH of the one-kidney animals and those of the two-kidney and sham groups (alpha = 0.05). Moreover, the mean norepinephrine content of the hypothalamus in the one-kidney animals was 66% greater than that of the two-kidney and sham groups (p < 0.05). These findings suggest that central noradrenergic pathways of the hypothalamus may be involved in the genesis of one-kidney renovascular hypertension.