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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is direct and indirect evidence that the kidneys are involved in the onset of hypertension in spontaneously hypertensive animals. In the Dahl strain, rather convincing evidence exists for a primary, inherent renal defect that is worsened by high dietary salt. In the Okamoto and New Zealand strains, an intrinsic defect may be provoked by increased sympathetic nerve activity. Similarities between all of these strains and Goldblatt hypertension suggest a fluid volume abnormality, but the gradual onset of elevated pressure and continuing growth during development of hypertension may obscure critical volume changes. Theoretically, arterial pressure, somewhat independent of intermediate steps, will reach the level which is dictated by renal function as being necessary for the maintenance of salt and water homeostasis. While widespread use of different spontaneously hypertensive strains may currently be complicating our understanding of the intermediate steps, studies of dissimilar strains should, in time, enhance our understanding of the many different facets of long-term blood pressure control.
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PMID:The role of the kidney in spontaneous hypertension. 108 11

To test the hypothesis that renin is circulating in pressor amounts in renal hypertension, two-kidney Goldblatt hypertension was produced in rats. After hypertension had been present for a variable period of time (4 to 21 days), the ischemic kidney was removed, and an infusion of rat renin was started immediately to replace the endogenous renin that the ischemic kidney had been releasing. Since the amount of renin released by the clipped kidney was not known, the amount infused was regulated by a feedback mechanism set to keep the mean blood pressure at the same level as before ipsilateral nephrectomy. Hypertension remission was therefore prevented by this procedure. The PRA at the end of the renin infusion was similar to that prior to the ipsilateral nephrectomy. This finding indicates that the levels of the PRA circulating in renal hypertension are within the pressor range, thus supporting the hypothesis that renin plays a role in the pathogenesis of the acute or semiacute phase of renal hypertension. However, the participation of other factors cannot be ruled out since no correlation was found between PRA and blood pressure.
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PMID:Role of renin in the pathogenesis of renal hypertension. 113 78

An angiotensin II inhibitor was administered to rats with two-kidney Goldblatt hypertension. The inhibitor produced a marked drop in blood pressure after 5 weeks but no significant change after 15 weeks of hypertension. However, even after 15 weeks of hypertension, following sodium depletion by either diuretics or a low sodium diet, the animals again became renin dependent as readministration of the inhibitor induced a significant fall in blood pressure. The data indicate that two-kidney Goldblatt hypertension is initially renin dependent but subsequently becomes sodium volume dependent in a way similar, although more protracted, to that already described for one-kidney Goldblatt hypertension.
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PMID:Reciprocation of renin dependency with sodium volume dependency in renal hypertension. 114 99

Increasing interest has been directed toward the possible role of trophically acting molecules as modulators or initiators, or both, of myocardial hypertrophy. The aim of the present study was to investigate the possible role of one such molecule, namely, insulin-like growth factor I, in myocardial hypertrophy developed in response to renal artery stenosis. Two-kidney, one clip Goldblatt hypertension was induced in Wistar rats weighing 180 g, and sham-operated animals were used as controls. Blood pressure was increased as early as 2 days after clipping (133 +/- 4 versus 116 +/- 4 mm Hg, p less than 0.05), and the increase persisted 4 and 7 days after clipping (148 +/- 6 versus 129 +/- 3 mm Hg, p less than 0.01 and 171 +/- 5 versus 139 +/- 3 mm Hg, p less than 0.01, respectively). Left ventricular weight followed a similar pattern (373 +/- 7 versus 350 +/- 8 mg, NS, 415 +/- 11 versus 386 +/- 9 mg, p less than 0.01, and 466 +/- 11 versus 391 +/- 10 mg, p less than 0.01 at 2, 4, and 7 days after clipping, respectively), but no changes in body weight between the groups were observed. Insulin-like growth factor I messenger RNA (mRNA) was quantified using a solution hybridization assay. After 4 days of renal hypertension, there was a significant increase in left ventricular insulin-like growth factor I mRNA (2.0 x 10(-18) +/- 0.48 x 10(-18) versus 0.4 x 10(-18) +/- 0.07 x 10(-18) mol.microgram DNA-1), which was no longer detectable 7 days after clipping.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Jan
PMID:Left ventricular insulin-like growth factor I increases in early renal hypertension. 137 Apr 28

To evaluate the contribution of systemic hypertension in the progression of nephropathies to glomerular sclerosis, a mild form of puromycin aminonucleoside (PAN) nephrosis was associated with Goldblatt hypertension and studied after 18 weeks. We studied four groups: Group I, controls; Group II, Goldblatt hypertension; Group III, PAN nephrosis; and Group IV, both conditions. Systolic blood pressure, 24-h proteinuria, serum cholesterol, triglycerides, glomerular hemodynamics, and histological studies were compared among the groups. Rats in groups II and IV developed systemic hypertension, but only group IV rats showed persistent proteinuria. No alterations in lipid metabolism were present in any of the groups. The most striking findings in the micropuncture studies were a significant increase of glomerular capillary pressure in group IV rats (63.15 +/- 1.34 mm Hg) as compared to controls (48.74 +/- 0.97 mm Hg) and to groups II and III (55.31 +/- 2.11 and 48.17 +/- 1.23 mm Hg, respectively), and a marked fall in Kf in groups III and IV. Only group IV showed significant histological alterations such as glomerular sclerosis, interstitial damage, and increased glomerular area. These results suggest that, in the presence of an underlying nephropathy, a greater fraction of systemic pressure is transmitted to the glomerular capillaries when systemic hypertension is present; the resulting elevation in glomerular pressure and proteinuria seems to be responsible for the progression to glomerular sclerosis.
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PMID:Mechanisms involved in the progression to glomerular sclerosis induced by systemic hypertension during mild puromycin aminonucleoside nephrosis. 141 51

To analyze the determinants of left ventricular (LV) performance (myocardial afterload, chamber size, mass, and contractility) in Goldblatt hypertension, 19 anesthetized one-kidney, one-clip (1K1C) and 28 two-kidney, one-clip (2K1C) male Wistar rats were studied 58 to 62 days after clipping, together with 19 sham-operated and 13 normal rats (controls), by M-mode echocardiography using necropsy-validated methods of measurement. The LV fractional shortening was inversely related to end-systolic stress in all groups (r = -0.89 to -0.95, all P less than .00001): 7 2K1C (25%) and 9 1K1C (47%) had fractional shortening above the upper confidence limit in control animals. Both 1K1C and 2K1C with high LV performance had severe hypertension, inadequate LV hypertrophy, with resultant high wall stress (both P less than .005), increased LV chamber dimension (P less than .005 and P less than .05, respectively) and high afterload-corrected fractional shortening (both P less than .001); 2K1C also had high plasma renin activity and atrial natriuretic factor levels (both P less than .01). Rats with normal LV performance exhibited mild hypertension, adequate LV hypertrophy (normalizing wall stress), and normal LV chamber size and afterload-corrected fractional shortening. Thus, 8 1/2 weeks after clipping, adequate LV hypertrophy allows maintenance of normal LV function by normalizing myocardial afterload in a majority of rats with Goldblatt hypertension, whereas increased LV contractility (and possibly use of preload reserve in 1K1C) maintains normal LV function in the presence of inadequate LV hypertrophy and elevated wall stress, in a substantial minority of rats that developed more severe Goldblatt hypertension.
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PMID:Relation of left ventricular hypertrophy, afterload, and contractility to left ventricular performance in Goldblatt hypertension. 153 70

We tested the hypothesis that endothelium-dependent afferent arteriolar vasodilation is impaired in the nonclipped kidney of two-kidney, one clip Goldblatt hypertensive rats relative to sham-operated controls. Five to six weeks after positioning of a 0.25-mm clip on the left renal artery, systolic pressure averaged 173 +/- 10 mm Hg in Goldblatt rats and 118 +/- 4 mm Hg in controls (p less than 0.01). The right kidney was harvested for videometric study of the microvasculature using the in vitro blood-perfused juxtamedullary nephron technique. Kidneys from Goldblatt and control rats were perfused at renal arterial pressures of 150 and 110 mm Hg, respectively. Afferent arteriolar inside diameter did not differ between control (20.3 +/- 0.7 microns) and Goldblatt (21.1 +/- 1.7 microns) kidneys. Determination of afferent responses to increasing concentrations of the endothelium-dependent vasodilator acetylcholine (1 nM to 10 microM) in the bathing solution unveiled a shift to the right in the dose-response relation in Goldblatt rats. Afferent arterioles from control kidneys dilated significantly when exposed to 1 nM acetylcholine, whereas a 1,000-fold higher concentration was required to dilate arterioles from Goldblatt rats. Sodium nitroprusside, an endothelium-independent vasodilator, increased afferent diameter to a similar extent in both groups. In a separate group of normal kidneys, vasodilator responses to 10 microM acetylcholine were completely blocked by 1,000 microM nitro-L-arginine, an inhibitor of nitric oxide synthesis. Thus, endothelium-dependent afferent vasodilation appears to be impaired in the nonclipped kidney of Goldblatt hypertensive rats. This phenomenon could contribute to the altered renal hemodynamic status characteristic of Goldblatt hypertension.
Hypertension 1992 Jun
PMID:Attenuated afferent arteriolar response to acetylcholine in Goldblatt hypertension. 159 81

We have previously demonstrated that loss of renal functional reserve (renal response to protein loading) in two-kidney, one clip Goldblatt hypertension is characterized by no change in glomerular filtration rate or single nephron glomerular filtration rate and decreased absolute proximal tubular reabsorption during glycine administration. Captopril restores proximal reabsorption and renal functional reserve in this condition. Because captopril suppresses angiotensin II generation and increases bradykinin, prostaglandins, and potentially nitric oxide, we have investigated the role of angiotensin II blockade in restoring proximal reabsorption and renal functional reserve by comparing captopril with DuP 753, an angiotensin II receptor antagonist, in Goldblatt rats. One month after clipping, two period micropuncture studies (control and glycine) were performed on the unclipped kidney. Normal rats and three groups of clipped rats were studied: an untreated group (HYP), a group treated with captopril (CEI), and a group treated with DuP 753 (DuP) 5 days before micropuncture. Glycine increased glomerular filtration rate, nephron plasma flow, and single nephron glomerular filtration rate in normal rats. Systemic and glomerular hypertension in HYP rats was associated with loss of renal functional reserve and a decrease in absolute proximal reabsorption during glycine. Captopril and DuP 753 normalized systemic and glomerular capillary pressure and prevented the decrease in proximal reabsorption during glycine; however, only CEI rats increased single nephron glomerular filtration rate and glomerular filtration rate after glycine. In conclusion, abnormal responses of both glomerular and tubular function are responsible for the loss of renal functional reserve in Goldblatt rats. Inhibitory angiotensin II activity is responsible for decreasing proximal reabsorption during glycine; however, factors other than angiotensin II limit the glomerular response to glycine.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1992 Jun
PMID:Angiotensin II and renal functional reserve in rats with Goldblatt hypertension. 159 82

In a series of animal studies we have clearly demonstrated since 1970 that calcium overload of the arterial wall is crucially involved in the pathogenesis of arteriosclerotic lesions. Following excessive calcium uptake, vascular stretch compliance and distensibility were lost together with structural integrity. Conversely, calcium antagonists that counteract abundant calcium uptake were found to prevent pathogenic mural calcium accumulation and damage. These effects were realized with light and electron microscopy as well as with measurements of calcium accumulation using atomic absorption spectrometry and radiocalcium. The experiments were carried out on rats exposed to various well-known risk factors such as nicotine, alloxan diabetes, high doses of vitamin D3, or dihydrotachysterol. Another particularly vasotoxic factor appeared to be hypertension, which develops in spontaneously hypertensive Okamoto rats (SHRs), in hypertensive NaCl-loaded salt-sensitive Dahl-S rats, and in rats with nephrogenic Goldblatt hypertension. Interestingly, aging arteries in animals and humans also exhibit, as a characteristic phenomenon, a steady increase in arterial calcium content. This natural age-dependent calcium accumulation is further enhanced in severe diabetics, heavy smokers, and hypertensive patients. However, the most excessive degree of toxic calcium overload, correlated with dramatic structural damage, occurred in human coronary artery plaques. Here, in "fatty streaks" (type I plaques according to World Health Organization classification), the mural calcium content exhibited a rise by 13 times above normal; in type II lesions (fibrous plaques), the increase in calcium was 24-fold; and in type III plaques, i.e., in "complicated lesions of stenosing character," calcium overload amounted to a value greater than 80 times above that found in healthy coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differentiation between calcium- and cholesterol-dominated types of arteriosclerotic lesions: antiarteriosclerotic aspects of calcium antagonists. 172 9

Dr. Skeggs demonstrated the lack of renin dependence in 1-kidney, 1-clip hypertension and elucidated some of the differences between that and Dr. Goldblatt's classic 2-kidney, 1-clip model of hypertension. Studies of these two different types of hypertension have led research in many new directions and helped to reveal the role of the renin-angiotensin system in hypertension and that system's interaction with sodium-induced vasodilation in both animals and humans. More recent research has investigated the processes behind essential hypertension and I present here the proposal that, due to nephron heterogeneity, essential hypertension in humans is parallel in its pathophysiologic processes to Goldblatt hypertension.
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PMID:On the mechanisms and clinical relevance of one-kidney, one-clip hypertension. 174 91


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