Increased sympathetic nerve activity in renovascular hypertension.
(9/715)
BACKGROUND: Increased sympathetic nerve activity may contribute to the progression of renovascular hypertension. Because previous results have been inconclusive, we investigated whether renovascular hypertensives show increased total and regional sympathetic nerve activity. METHODS AND RESULTS: Sixty-five patients underwent renal angiography and measurements of plasma renin activity and angiotensin II in conjunction with estimation of sympathetic nerve activity by means of radiotracer dilution and intraneural recordings of muscle sympathetic nerve activity (MSNA). Age-matched healthy subjects (n=15) were examined for comparison. Total body norepinephrine (NE) spillover, an index of overall sympathetic nerve activity, was increased by 100% and MSNA by 60% in the hypertensive patients compared with healthy subjects (P<0.01 for both). A subgroup of 24 patients with well-defined renovascular hypertension (cured or improved hypertension after renal angioplasty) showed similar increases in total body NE spillover compared with the group at large. Patients with arterial plasma renin activity and angiotensin II levels above median had higher values for total body NE spillover than patients below median (P<0.01). CONCLUSIONS: This study unequivocally demonstrates elevated sympathetic nerve activity in patients with renovascular hypertension. The adrenergic overactivity may contribute to the blood pressure elevation and perhaps also to the high cardiovascular mortality in renovascular hypertension. (+info)
Protective role of the angiotensin AT2 receptor in a renal wrap hypertension model.
(10/715)
We evaluated the role of the renal angiotensin II type 2 (AT2) receptor in blood pressure regulation in rats with 2-kidney, 1 figure-8 wrap (Grollman) hypertension. Renal wrapping increased systolic blood pressure (SBP). Renal interstitial fluid (RIF) bradykinin (BK), nitric oxide end-products (NOX), and cGMP were higher in the contralateral intact kidney than in the wrapped kidney. In rats with Grollman hypertension, losartan normalized SBP and increased renal function, RIF BK, NOX, and cGMP only in contralateral kidneys. In contrast, PD 123319, a specific AT2-receptor antagonist, significantly increased SBP and decreased RIF BK, NOX, and cGMP in both kidneys. Combined administration of losartan and PD 123319 prevented the decrease in SBP and the increase in RIF BK, NOX, and cGMP levels observed with losartan alone. BK-receptor blockade caused a significant increase in RIF BK and a decrease in RIF NOX and cGMP in both kidneys similar to that observed during administration of PD 123319. In rats that underwent sham operation, RIF BK increased in response to angiotensin II, an effect that was blocked by PD 123319. These data demonstrate that angiotensin II mediates renal production of BK, which, in turn, releases nitric oxide and cGMP via stimulation of AT2 receptors. The increase in blood pressure and the decrease in renal BK, nitric oxide, and cGMP during AT2-receptor blockade suggests that the AT2 receptor mediates counterregulatory vasodilation in Grollman hypertension and prevents a further increase in blood pressure. (+info)
Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function.
(11/715)
OBJECTIVE: Renovascular disease may lead to ischemia of the nephrons and to fibrosis, which is generally considered to be irreversible and progressive. We investigated the potential of revascularization to recover and stabilize renal function in patients with ischemic nephropathy. METHODS: In a retrospective analysis of all our 61 patients with ischemic nephropathy who underwent treatment with surgical revascularization, we determined the long-term course of renal function decline with an estimated glomerular filtration rate (EGFR; Cockcroft and Gault formula). With the assumption of normal renal function at age 25 years, the preoperative slope of EGFR and the postoperative slope of EGFR were determined from the EGFR before surgery, at the short-term follow-up examination (on average, 8 months after surgery), and at the long-term follow-up examination (on average, at 47 months after surgery). These declines in renal function were compared with EGFR values in age-matched and sex-matched samples from a large cross-sectional population study. RESULTS: The overall surgical mortality rate amounted to 13.1%. Five patients became dialysis dependent-two with preexisting end-stage renal disease and three at later follow-up examination-and two patients, who before surgery were dialysis dependent, could be withdrawn from dialysis treatment. Shortly after the operation, the mean EGFR level had increased from 28.3 to 43.1 mL/min/1.73 m2 ( P <. 01). The rate of decline in renal function had decreased from an estimated -2.57 mL/min/1.73 m2/year before surgery (weighted mean: interquartile range, -2.71 to -1.98) to -0.66 mL/min/1.73 m2/year (weighted mean: interquartile range, -2.00 to -0.18) in the short-term interval to the long-term interval, which was even slightly better than the slope of -0.84 mL/min/1.73 m 2/year in the age-matched and sex-matched control population. CONCLUSION: Surgical revascularization in selected patients with renovascular disease and ischemic nephropathy restores renal function and makes the average long-term rate of decline in renal function equal to that of the general population. This indicates that in most patients a "point-of-no-return" has not yet been passed even though their renal function is already markedly impaired before surgery. Therefore, in well-selected patients with ischemic nephropathy, considerable improvement of renal function can be realized. (+info)
PDGF-A expression correlates with blood pressure and remodeling in 1K1C hypertensive rat arteries.
(12/715)
We previously demonstrated remodeling of large and small arteries in angiotensin II-treated rats, paralleled by an increased expression of platelet-derived growth factor (PDGF)-A chain mRNA in large arteries. Both remodeling and PDGF-A expression were associated with elevation of blood pressure rather than a direct effect of angiotensin II. To further delineate the role of PDGF-A and elevated blood pressure, we assessed the level of PDGF-A and -B mRNA and protein in the wall of large as well as small arteries in the one-kidney, one-clip (1K1C) hypertensive rat, a non-renin-dependent model of hypertension. Fourteen days after renal artery stenosis, the thoracic aorta and both femoral arteries were collected from 1K1C rats (n = 8) and uninephrectomized controls (n = 8) and immediately processed for morphological measurement, immunohistochemistry, RT-PCR, and Western blotting. Systolic blood pressure was significantly elevated in hypertensive rats (202 +/- 26 mmHg) compared with control rats (122 +/- 7.9 mmHg) and was accompanied by arterial hypertrophy in both aorta and femoral arteries. The mRNA for PDGF-A chain was increased threefold in the thoracic aorta (P < 0.05) of 1K1C rats, whereas the message for PDGF-B was not significantly changed in hypertensive versus control animals. A higher staining of the intima-media was observed by using an anti-PDGF-A chain polyclonal antibody on paraffin-embedded sections. Western blot results indicated an approximately 2-fold increase in PDGF-A protein in aortic and femoral wall of the 1K1C rats. The results showed that both the mRNA and protein for PDGF-A chain are increased and well correlated with the blood pressure and wall area, suggesting a direct effect of elevated pressure on PDGF synthesis, which, in turn, may affect the onset and progression of vascular hypertrophy. (+info)
Experimental model of renovascular hypertension.
(13/715)
OBJECTIVE: To establish a model of renovascular hypertension. METHODS: A 4/0 resorbable chromic catgut ligature was used to ligate subtotally the renal arteries of 18 dogs, forming experimental renovascular hypertension steadily. Blood pressure, plasma renin activity, the ultrastructural changes of juxtaglomerular apparatus and renal artery wall were studied after the constriction. RESULTS: It was reasonable that renal blood flow measured with an electromagnetic flowmeter was reduced by 30% after the constriction. The pathological changes of the induced renal artery stenosis were similar to those of fibromuscular dysphasia. CONCLUSION: The findings provide valuable evidence for the treatment of renovascular hypertension. (+info)
Noninvasive evaluation of a novel swine model of renal artery stenosis.
(14/715)
Intrarenal hemodynamics and excretory function distal to renal artery stenosis are difficult to quantify noninvasively. In this study, a swine model of chronic unilateral renal artery stenosis, achieved by implantation of an intravascular device that leads to a gradual and progressive luminal area narrowing, was developed and evaluated. Bilateral cortical and medullary volumes, blood flows, and segmental tubular dynamics were assessed in the intact kidneys of seven pigs using electron-beam computerized tomography before and 1 mo after implantation of the device. Within 1 mo, a 66% angiographic stenosis was significantly correlated with a 25% increase in BP. The volume and blood flow were markedly lower in the stenotic compared with the contralateral kidney and cortex, while the medulla exhibited minimal changes. In the stenotic kidney, intratubular contrast content has decreased in all nephron segments, especially in the distal tubule, where it correlated with an increase in serum creatinine and stenosis severity. In the contralateral kidney, dilution of proximal tubular fluid correlated with the increase in BP, likely due to pressure-natriuresis. In conclusion, the swine model closely resembles human renovascular hypertension. In the stenotic kidney, the hemodynamic impairment of the cortex is dissociated from the relatively preserved renal medulla, and the earliest effect on excretory function is observed in the distal nephron, where the fall in the amount of fluid reaching that segment is directly proportional to the renal arterial compromise. Electron-beam computerized tomography shows promise to noninvasively quantify, follow-up, and study changes in concurrent, in vivo intrarenal hemodynamics and segmental tubular function in renovascular hypertension. (+info)
Cyclooxygenase-2 inhibition decreases renin content and lowers blood pressure in a model of renovascular hypertension.
(15/715)
It has been proposed that the macula densa participates in the regulation of increased renin expression in renovascular hypertension (RVH) and that prostaglandins may be among the mediators of macula densa function. We have previously shown that in renal cortex, cyclooxygenase-2 (COX-2) expression is localized to the macula densa and surrounding cortical thick ascending limb and increases in high-renin states, such as salt restriction and angiotensin-converting enzyme inhibition. In the present studies, we examined the effect of the selective COX-2 inhibitor SC58236 on plasma renin activity (PRA) and renal renin expression in RVH in rats. The aorta was coarcted between right and left renal arteries, and animals received either SC58236 or vehicle for 1 week. At day 8, vehicle-treated coarcted rats were hypertensive (mean carotid arterial blood pressure: 138+/-3 versus 87+/-2 mm Hg in sham-operated controls; n=9 to 11; P<0.001) and exhibited a disparity of kidney size (ratio left/right kidney: 0.78+/-0.04 versus 1.02+/-0.02; n=9 to 10; P<0.001). PRA increased significantly (84.6+/-6.5 versus 9.0+/-1.4 ng angiotensin I [Ang I] per milliliter per hour; n=8 to 9; P<0.01). In the coarcted rats, neither renin mRNA expression nor renin activity of the right kidney was altered (renin/GAPDH mRNA: 1.12+/-0.05-fold levels in control rats; n=6; P=NS; renin activity: 23.4+/-1.8 versus 27.1+/-3.4 ng Ang I per hour per milligram protein; n=8 to 9; P=NS). However, the renin mRNA of the left kidney increased to 3.0+/-0.6-fold of control (n=6), and the renin activity increased to 189.0+/-28.6 ng Ang I per hour per milligram protein (n=8; P<0.01). Expression of COX-2 mRNA and immunoreactive protein increased in the affected left kidney but was not different from control in the unaffected right kidney. SC58236 treatment to coarcted rats did not affect kidney size (ratio left/right kidney: 0.79+/-0.06; n=9). However, PRA was significantly decreased compared with the vehicle-treated coarcted rats (19.8+/-2. 8 ng Ang I per milliliter per hour; n=9; P<0.01). The left kidney renin mRNA and renin content were also decreased (1.7+/-0.3-fold control; n=6; P<0.05; and 45.7+/-7.6 ng Ang I per hour per milligram protein; n=9; P<0.01, respectively), while renin mRNA and renin content of the right kidney were not altered. SC58236 lowered mean arterial blood pressure (122+/-5 mm Hg; n=14; P<0.05 compared with vehicle). A significant correlation was observed between PRA and mean blood pressure (r=0.75; P<0.01). In summary, these studies indicate that the selective COX-2 inhibitor SC58236 decreases renin production and release in RVH and suggest an important role for COX-2 regulation of the renin-angiotensin system. (+info)
The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension.
(16/715)
In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1. 0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n = 10). Myocardial histology was analysed in 3 microm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension. (+info)