Two-kidney Hypertension Research Articles

Expression of MMP-9 and the intervention effect of telmisartan on vascular remodeling of 2K1C Hypertension Rats

Objective To explore the expression and mechanisms of MMP-9 in vascular remodeling of two-kidney and one-cliped hypertension rats. Methods Male Wistar rats were randomly divided into sham operation group( n = 10), two-kidney and one-clip model (2KIC) group ( n = 10) and telmisartan group ( n = 7 ). Telmisartan group were injected with telmisartan every day. The blood pressure was determined every week. The morphologic change of carotid artery and thoracic aorta was observed with HE stainning 8 weeks after treatment with telmisartan.Arteries was performed to evaluate the expression of MMP-9 with immunohistochemisty. Results The blood pressure,vessel wall,and the expression of MMP-9 in model group were significantly higher than that of control group.Telmisartan nearly normalized arterial pressure and suppressed all these changes. Conclusion MMP-9 was related to vascular remodeling and Telmisartan could regulate vascular remodeling in 2-kidney and 1-cliped hypertension rats by inhibiting the pathway of MMP-9. Key words: MMP-9 ; 2K1 C, Hypertension; Vascular Remodeling ; Telmisartan

Partial transfer of genetic hypertension by lymphoid cells in Lyon rats

The involvement of immune factors in a given disease is suggested by evidence that a disease can be prevented by immunosuppression and can be transferred by lymphoid cells. Because the first type of experimental result was achieved in Lyon hypertensive (LH) rats, the present study was undertaken to determine whether hypertension can be transferred to normotensive recipients. As a control, the blood pressure effects of lymphoid cell grafts from renovascular hypertensive donors were also determined. Splenocytes and lymph node cells from LH and Lyon low-blood pressure (LL) rats with two-kidney Goldblatt hypertension were respectively injected into LH x Lyon normotensive (LN) F1 hybrids and LL rats aged 7, 8, 9 and 10 weeks. Blood pressure was measured by plethysmography from age 6 to 13 weeks and an intra-arterial recording was performed in 14-week-old conscious rats. Lymphoid cell injections from LL rat donors with two-kidney hypertension did not modify the blood pressure of LL rat recipients. In contrast, lymphoid cell grafts from LH rat donors induced a significant increase in blood pressure in F1 recipients compared with control F1 rats after the first injection. As confirmed by intra-arterial recording, this blood pressure effect lasted until age 14 weeks (145 +/- 1 versus 137 +/- 1 mmHg in grafted and ungrafted F1, respectively). It was not related to alterations in the acute role of the renin-angiotensin and sympathetic nervous systems and was not associated with increased pressor responses to the vasoconstrictor drugs tested. The present study demonstrates that genetic hypertension can be partially transferred by lymphoid cells in F1 recipients. The effect seems to be specific to genetic hypertension because lymphoid cells from renovascular hypertensive donors failed to transfer this secondary form of hypertension. The present results support the hypothesis that cellular immune reactions contribute to the pathogenesis of hypertension and LH rats.

High Salt Intake Attenuates the Development of Hypertension in Two-Kidney, One-Clip Goldblatt Rats

Effects of high salt intake on the early onset of hypertension were examined in two-kidney, one-clip rats. They were divided into high salt and control groups which were supplied with 1.0% NaCl and tap water, respectively, as a drinking solution for 12 days after clipping the left renal artery. The high salt group showed a lower plasma renin concentration and a higher plasma atrial natriuretic peptide (ANP) along with an attenuation of the magnitude of early hypertension, as compared with the control group. A significant positive correlation between blood pressure and plasma renin concentration and an inverse correlation between plasma renin concentration and ANP were shown. Cortical renal renin content was comparable between the two groups. In another two groups of sham-clipped rats, the high salt group did not differ from the tap water-drinking group in any of the parameters examined, except that ANP was significantly higher. These results demonstrate that high salt intake attenuates the developmental phase of hypertension in two-kidney, one-clip rats by increasing the ANP and suppressing the release of renin.

Renovascular hypertension: Etiology and pathophysiology

Evidence from animal studies demonstrates that the renin-angiotensin (ANG II) system and sodium retention play major roles in experimental renovascular hypertension (RVH). Two basic models have been described. In the first, one-clip two-kidney Goldblatt hypertension, the ischemic kidney secretes renin, which leads to increased ANG II formation and hence elevation of blood pressure (BP). As BP rises, sodium excretion by the intact contralateral kidney increases (pressure natriuresis); therefore, there is no sodium retention. In the second, one-clip one-kidney Goldblatt hypertension, the contralateral kidney is removed. In this case the pressure natriuresis can no longer occur, and sodium retention occurs. The ensuing expansion of plasma volume inhibits renin secretion, so that in this model the renin level is normal or low. Following the clipping of the renal artery, renal blood flow and pressure are maintained distal to the stenosis by an ANG II-mediated vasoconstriction. This acts preferentially on the efferent glomerular arterioles, so that the ratio of preglomerular to postglomerular resistance is reduced, which helps to maintain glomerular filtration despite the reduced renal perfusion pressure. In the contralateral kidney the afferent arteriolar resistance is increased, probably as a direct result of exposure to the higher intrarenal arterial pressure. ANG II constricts the efferent arterioles in the same way as in the ischemic kidney, so that the ratio of preglomerular to postglomerular resistance is unchanged. When an angiotensin converting enzyme (ACE) inhibitor is given, the efferent arterioles vasodilate. In the ischemic kidney this may produce a reduction of glomerular filtration rate (GFR), which is not seen in the contralateral kidney. Unilateral RVH in humans corresponds closely to the animal model of one-clip two-kidney hypertension. Plasma renin activity is usually high, and converting enzyme inhibitors lower BP effectively. The increased renin is due exclusively to increased secretion of renin by the ischemic kidney, and is completely suppressed in the contralateral kidney. It is not clear whether bilateral RVH corresponds to the one-clip one-kidney model, but there is circumstantial evidence to suggest that both renin and volume factors may be involved. The majority of cases of human RVH are caused by atheroma, which is commonly bilateral, or by fibromuscular dysplasia. The former tends to be associated with atheroma elsewhere in the arterial tree, and often progresses to complete occlusion and renal failure. The latter occurs in younger patients, and almost never progresses to complete occlusion.

Endogenous opiate modulation of baroreflexes in normotensive and hypertensive rats.

It is evident that hypertension is associated with elevated endogenous opiates. This study was designed to examine the role of endogenous opiates in the development and/or maintenance of two-kidney renovascular hypertension and in baroreceptor reflex function in conscious hypertensive rats. Naloxone administration during the onset of hypertension significantly attenuated the rise in blood pressure. After one week, systolic blood pressure in naloxone-treated rats was 27 mmHg lower than in 0.9% NaCl-treated hypertensive rats. Acute naloxone infusions in chronic hypertensive animals also significantly lowered blood pressure (-10%) and heart rate (-26%). Baroreceptor function was significantly enhanced in both normotensive (+135%) and hypertensive (+207%) rats after administration of naloxone. Furthermore, naloxone treatment also caused the baroreflex response to shift from the higher reset state toward that seen in normotensive counterparts. The inability of naloxone methyl bromide to alter baroreflex sensitivity indicates that the site(s) of action of opiates resides in the brain. These data support a role for opiates in the development and/or maintenance of renovascular hypertension, which may be related to alterations in baroreceptor reflex function.

Cardiovascular studies in rats with respect to some functional and structural relationships of relevance in hypertension and ordinary aging.

Five current lines of cardiovascular studies in rats are outlined, mainly dealing with some functional and structural relationships of particular relevance for hypertension and ordinary aging: 1. Characteristics of the smooth muscles and their neurogenic control in 'Windkessel' arteries, conduit arteries, precapillary resistance vessels and venous capacitance vessels from normotensive rats (WKY) with comparisons to rats with primary hypertension (SHR). 2. Different types of structural renovascular adaptation, comparing aging with advancing SHR hypertension, with 'high-pressure' and 'low-pressure' kidneys in one-clip, two-kidney renal hypertension, and with hypertrophied kidneys in uni-nephrectomized normotensive rats. 3. Relationships between 'structural autoregulation', wall distensibility, vascular reactivity and smooth muscle sensitivity in SHR and WKY hindquarter resistance vessels along with aging. 4. Relationships between wall thickness, luminal dimension and contractility in left ventricles from SHR and WKY during aging, and when one-clip, two-kidney hypertension is superimposed. 5. Interference with the capacity of the neurohormonal mechanisms counteracting blood loss in rats when on chronic low-salt diet.

Effect of DOCA-salt on Angiotensin Dependency and Surgical Reversal of Hypertension in Two-kidney, One Clip Renal Hypertensive Rats

The development of hypertension in two-kidney, one clip renal hypertensive rats (2K, 1C RHR) was not altered by treatment with DOCA and saline solution as drinking fluid for two months of observation. However, the administration of DOCA and salt suppressed plasma renin activity (PRA), the renal renin content (RRC) of the clipped kidney and the response to a single oral dose of captopril (10 mg/kg). The weight of the contralateral kidney was increased by the administration of DOCA-salt, while that of the ischaemic kidney was not changed. The withdrawal of DOCA-salt treatment restored the PRA and the effects of captopril to a similar degree to the non-treated group. The acute hypotensive effects of captopril were reduced on the 10th week compared with the 7th week after renal arterial constriction in 2K, 1C RHR. The fall in blood pressure induced by captopril significantly correlated with the initial PRA both in the 7th and 10th week after clipping. There was a significant correlation between PRA and RRC of the clipped kidney. Rats previously treated with DOC-salt had either removal of the contralateral kidney with removal of the clip from the ischaemic kidney, or removal of the ischaemic kidney. Blood pressure fell to normal levels in the unclipped group and in the nephrectomy group, but the fall in the latter group was transient and within two weeks had risen to significantly higher levels than in the unclipped group. It is concluded that structural vascular change following DOC-salt hypertension is insufficient to cause persisting hypertension except when it occurs in the renal circulation.

What stimulates the renin-angiotensin system in rats with two-kidney renal hypertension?

1. Blood pressure, the hypotensive effect of captopril, plasma renin activity, renal renin content and kidney weight were measured in the two-kidney—one-clip model, the one-kidney—one-clip model and the two-kidney—one-clip model with the ureter of the contralateral kidney ligated in rats. The ureteric ligation was performed to abolish urinary excretion from the contralateral kidney in the two-kidney—one-clip model. 2. The development of hypertension after renal artery constriction was earlier and greater in the one-kidney—one-clip model and the two-kidney—one-clip model with ureter of the contralateral kidney ligated than in the two-kidney—one-clip model. A single oral dose of captopril produced a greater fall in blood pressure in both the two-kidney models than in the one-kidney—one-clip group. 3. Plasma renin activity and renal renin content of the clipped kidney were higher in the two-kidney model rats, whether or not the ureter had been ligated, than in the one-kidney—one-clip model animals, although more than half the rats from the two-kidney model had normal values. There was a significant correlation between plasma renin activity and the response to captopril in all groups, whereas in none of the three groups was the correlation between plasma renin activity and blood pressure significant. 4. The clipped kidney had a higher renin content than did the contralateral kidney, and the weight of the ischaemic kidney was decreased compared with the contralateral kidney whether it was untouched or had its ureter ligated. The weight of the clipped kidney was in the order one-kidney—one-clip model > two-kidney—one-clip model with ureter of the contralateral kidney ligated > two-kidney—one-clip model. 5. It was concluded that the renin-angiotensin system was stimulated to the similar degree in some animals for the two-kidney—one-clip models, whether or not the ureter of the contralateral kidney had been ligated, compared with the one-kidney—one-clip animals. This finding suggests that the contralateral kidney can stimulate renin secretion and synthesis in the clipped kidney independently of Na+ excretion.

Angiotensin-converting enzyme activity of the brain and the aorta in experimental hypertensive rats.

Angiotensin-converting enzyme activity in six areas of the brain (cerebral cortex, midbrain, thalamus, hypothalamus, striatum, and cerebellum) and subcellular fractions of the aorta (homogenate, mitochondria, microsomes, and supernatant) was determined in both normotensive and renal hypertensive rats [Goldblatt one-clip, one-kidney (1-c, 1-k) and one-clip, two-kidney (1-c, 2-k) hypertensive, and two-clip, two-kidney (2-c, 2-k) hypertensive rats]. Converting-enzyme activity was relatively high in the thalamus and relatively low in the cerebellum in normotensive and renal hypertensive rats. The enzyme activity in the hypothalamus of Goldblatt 1-c, 2-k rats was significantly higher than that of normotensive and other renal hypertensive rats. However, there was no significant difference in the enzyme activity in each brain area among normotensive, Goldblatt 1-c, 1-k hypertensive and 2-c, 2-k hypertensive rats. The enzyme activity of the supernatant from aortic subcellular fractions was extremely high in normotensive and renal hypertensive rats. However, the enzyme activity in all aortic fractions from Goldblatt 1-c, 2-k rats was significantly higher than that of normotensive and other renal hypertensive rats. There was no significant difference in the enzyme activity among normotensive, Goldblatt 1-c, 1-k hypertensive and 2-c, 2-k hypertensive rats. Therefore, it is likely that increased angiotensin-converting enzyme activity in the brain and the aorta may play a role in the initiation or the maintenance of hypertension in Goldblatt 1-c, 2-k hypertensive rats.

Effects of indomethacin in dogs with acute and chronic renovascular hypertension.

This study examines the role that prostaglandins play in both the developmental and chronic phases of renovascular hypertension. Two 5-mg/kg doses of indomethacin were given to conscious dogs with renal denervation and receiving propranolol during the acute and chronic phases of one-kidney (1-KHT) and the acute phase of two-kidney (2-KHT) renovascular hypertension. Indomethacin produced striking reductions in plasma renin activity from the high level observed during the acute phase of both 1-KHT and 2-KHT. However, plasma renin activity failed to return to normal, and the hypertensive level of pressure decreased only slightly. In the chronic 1-KHT dogs, indomethacin did not lower plasma renin activity or mean arterial blood pressure unless plasma renin activity was elevated above the normal level. Also, indomethacin failed to alter renal function during the acute phase of 1-KHT but effective renal plasma flow fell during chronic 1-KHT. These results suggest that, in the dog, renal prostaglandins are involved in the pathogenesis of both acute 1-KHT and 2-KHT, whereas the role of renal prostaglandins in the regulation of arterial pressure appears to be negligible in chronic 1-KHT except during superimposed sodium depletion or severe hypertension. The data indicate that prostaglandins are involved in renovascular hypertension in the dog only under conditions where plasma renin activity is elevated. It is suggested that the release of renin after renal artery constriction is mediated by the vascular receptor that is at least partially independent of renal prostaglandin synthesis.

Angiotensin II and renal hypertension in dog, rat and man: effect of converting enzyme inhibition.

The role of the renin-angiotensin system in the pathogenesis of one-clip, two-kidney hypertension has been studied in man, dog and rat. Particular attention has been paid to peripheral plasma concentrations of angiotensin II in different circumstances; angiotensin II infusion has been combined with radioimmunoassay to construct angiotensin II/blood pressure dose-response curves. The effect of converting enzyme inhibitors has been studied, precautions being taken to avoid obtaining falsely high values for plasma angiotensin II because of cross-reaction with angiotensin I in these circumstances. The initial phase of one-clip, two-kidney hypertension is attributable to the direct pressor effect of the immediate rise in plasma angiotensin II. Subsequently, plasma angiotensin II is relatively lower, although blood pressure remains high. This upward resetting of the plasma angiotensin II/blood pressure relationship can be mimicked by infusing angiotensin II chronically at low dose. After reconstruction of a stenosed renal artery, or excision of a post-stenotic kidney, the angiotensin II/blood pressure relationship returns slowly to normal. In this second phase of one-clip, two-kidney hypertension, the long-term administration of saralasin, or of converting enzyme inhibitor, can also return arterial pressure to normal; brief administration of these drugs is less effective or ineffective. The results are compatible with, although they do not conclusively establish, an important slow pressor action of the renin-angiotensin system in the second phase of one-clip, two-kidney hypertension. This provides a rational basis for the use of captopril clinically in this condition.

Humoral and neurogenic factors in two-kidney renovascular hypertension.

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.

Exchangeable sodium in angiotensinogenic and nonangiotensinogenic renovascular hypertension.

Previous studies have suggested that angiotensin II and sodium can act as alternative mechanisms in maintaining high blood pressure in chronic renovascular hypertension, In the present study, exchangeable sodium was measured in rats in which angiotensin II has been confirmed or excluded as the main cause of the hypertension. To determine the degree of participation of angiotensin II in the maintenance of the high blood pressure, we studied the mean blood pressure response to an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) and to a converting enzyme inhibitor (SQ20,881). Rats with a decrease in blood pressure of less than 20 mm Hg, in response to both inhibitors, were classified as nonresponders; those with a decrease of 20 mm Hg or more, as responders. Fifty percent of the rats with two-kidney hypertension were nonresponders, and they had lower blood pressure and plasma renin activity than the responders. Further, these two-kidney, hypertensive, nonresponder rats had normal exchangeable sodium. The two-kidney hypertensive responders, on the other hand, had significantly higher exchangeable sodium than both the two-kidney, hypertensive nonresponders and the two-kidney control rats. These results suggest that angiotensin II and exchangeable sodium do not play a major role in the maintenance of the high blood pressure in the two-kidney hypertensive nonresponders. However, there appears to be an abnormal relationship between renin and exchangeable sodium in the two-kidney hypertensive responders that could contribute to the maintenance of the hypertension.

Neurogenic activity--angiotensin II interaction during the development and maintenance of renal hypertension in the rat.

1. Pentolinium tartrate (a ganglionic blocker) was injected in conscious rats during the early and late phases of two-kidney renal hypertension produced by aortic ligation. 2. In the early phase ( 5 days after aortic ligation), ganglionic blockade resulted in a decrease in blood pressure equal to that obtained in normotensive rats. Later, at days 12 and 40, for equally severe hypertension, ganglion blockade resulted in a greater decrease in blood pressure. 3. A 30 min infusion of [Sar1, Ala8]angiotensin II during the pentolinium-induced nadir in blood pressure resulted in a further decrease in blood pressure at day 5. Later, at days 12 and 40, this effect was smaller. 4. A 300 min infusion of [Sar1, Ala8]angiotensin II normalized the blood pressure in hypertensive rats at day 40. This delay response may be secondary to a central effect of the antagonist, reducing neurogenic tone or peripheral antagonism of locally generated angiotensin II in the blood vessel walls. 5. At day 40, removal of the small left kidney resulted in a greater decrease in blood pressure. This suggests the presence of a renal factor other than renin in the chronic phase of this hypertension.

Circadian changes in plasma renin activity and plasma aldosterone concentration in two-kidney hypertension rats.

Circadian changes in plasma renin activity (PRA) and plasma aldosterone concentration (PAC) in normal and hypertensive rats were determined by measurements at 8 a.m., 4 p.m. and 12 midnight (MN). For the normals, PRA and PAC were highest at 4 p.m. Animals made hypertensive by constriction one renal artery with the other kidney intact were studied after 4, 5, 7 and 10 weeks; the clear-cut circadian rhythm for PRA in normals had disappeared but for PAC the circadian rhythm was present in the 4-, 5- and 10-week groups. Both PRA and PAC were elevated in all four hypertensive groups compared with the normal controls and there was a highly significant correlation between PRA and PAC. The 4 p.m. peak value for PAC was much higher in relation to the 8 a.m. and 12 MN values values in the hypertensive animals than in the normals. Sodium balance studies failed to demonstrate any appreciable differences among the groups. When the hypertensive animals were divided into two groups on the basis of the level of hypertension, the rats with moderate hypertension showed an average elevation in PRA which was significant in only the 4- and 7-week groups whereas PRA was elevated in all four groups with severe hypertension. Thus, the present data help to define the activity of the renin-angiotensin-aldosterone system in two-kidney, one clip hypertension in the rat.

高血圧と脳血管

The present report dealt with hypertrophy and acute vascular lesions of cerebral arterioles in hypertensive rabbits. Hypertension was produced by clipping of the renal artery with intact contralateral kidney (two-kidney hypertension) or with contralateral nephrectomy (one-kidney hypertention).(1) Wall areas of cerebral arterioles were measured in 47 animals which had been killed one week after clipping of the renal artery (two-kidney hypertension) or sham-operation. The wall areas were calculated from the external and internal diameter of arterioles in hypocampus on coronal sections of the brain. The incidence of arterioles with greater wall areas was significantly increased in hypertensive animals as compared with normotensive ones. These results indicate that hypertrophy of cerebral arterioles develops already in the early stage of hypertension.(2) Acute vascular lesions and increase in vascular permeability were studied in one-kidney hypertensive rabbits with or without cerebral hemorrhage. Colloidal carbon technique was used to detect increase in vascular permeability. Necrotic changes of cerebral arterioles were found in 14 of 18 animals with cerebral hemorrhage, but was found in none of 15 animals without it. Arteriolar necrotic changes of other organs were frequently found in both animals with and without cerebral hemorrhage. Increase in vascular permeability of arterioles was more widely distributed than the necrotic changes. Vascular permeability was increased not only in arterioles but also in larger arteries including aorta and carotid artery in some of animals with cerebral hemorrhage.

Effects of central and peripheral angiotensin blockade in hypertensive rats.

The angiotensin II (AII) antagonist [Sar1-Ala8]AII (Saralasin) was injected into the brain ventricles (IVT) and intravenously (IV) in five different types of hypertensive unanesthetized rats. Renal hypertension was studied 16-22 days after kidney clipping. Intravenous infusions of cumulative doses (0.1-100 microgram/kg per min) and IVT injections (5-40 microgram) of Saralasin did not change mean arterial pressure (MAP) in controls and in one-clip, one-kidney Goldblatt hypertension, whereas MAP decreased in one-clip, two-kidney Goldblatt hypertension following IV and IVT Saralasin. In two-clip, two kidney hypertensive rats, IVT Saralasin decreased MAP but was ineffective when infused IV. Both IV and IVT Saralasin increased MAP in DOC hypertension. In spontaneously hypertensive (SH) rats, IV Saralasin increased MAP; IVT injection decreased MAP. The effect of IVT Saralasin in SH rats persisted 15-20 h after nephrectomy. We conclude that plasma AII may contribute to peripheral and central mechanisms of blood pressure regulation. The dissociation of the effects of IV and IVT Saralasin and the persistance of blood pressure decrease in nephrectomized SH rats following IVT Saralasin further support a role for locally formed brain angiotensin.

CORRECTION OF RENAL HYPERTENSION IN THE RAT BY PROLONGED INFUSION OF ANGIOTENSIN INHIBITORS

Injection of saralasin or converting-enzyme inhibitor produced a small variable reduction of blood-pressure in rats with two-kidney hypertension. Prolonged infusion of the inhibitors gradually reduced blood-pressure to normal. Control infusions of saralasin in normal animals and of dextrose in normal and hypertensive animals did not reduce blood-pressure. Plasma-renin concentration correlated significantly with the early but not with the later fall of blood-pressure. Plasma-concentrations of renin and angiotensin II were closely related except in rats receiving converting-enzyme inhibitor, when angiotensin II was relatively reduced. The gradual reduction of arterial pressure by saralasin was not associated with increased urinary sodium excretion.

The course of arterial pressure and the effect of Sar1-Thr8-angiotensin II in a new model of two-kidney hypertension in conscious dogs.

1. We describe a new method of producing two-kidney hypertension in dogs by a two-step procedure with complete occlusion of a renal artery 2 weeks after it was partially constricted. 2. Control mean arterial pressure (96 +/- 3 mmHg) of nine conscious, trained dogs rose to 107 +/- 3 mmHg 2 weeks after partial constriction of a renal artery, and it stabilized at a sustained hypertensive plateau (124 +/- 7 mmHg) 3 weeks after complete occlusion. 3. Intravenous infusion of an angiotensin II antagonist (Sar1-Thr8-angiotensin II) caused arterial pressure to fall during the acute but not the chronic phase of renal hypertension. In this latter phase plasma renin activity had returned to control values. 4. We conclude that the renin-angiotensin system appears not to be directly involved in the chronic phase of two-kidney hypertension in the dog.

実験的高血圧における血漿レニン活性と血管障害

In order to clarify the roll of intrinsic renin in the development of hypertensive vascular lesions, plasma renin activity (PRA) and pathological findings were studied in two types of renovascular hypertension in rabbits.I. Short-term experiment.Hypertension was produced by constriction of left renal artery with an intact right kidney (two-kidney hypertension, Group A, 33 animals), and with right previous nephrectomy (one-kidney hypertension, Group B, 33 animals). Seven days after renal artery clipping, colloidal carbon was injected intravenously, and after one hour animals were sacrificed and examined light microscopically. PRA, serum Na, serum K, urea-N and hematocrit were determined before and after the operation.Hypertension developed in both A and B groups similarly. Increased PRA, hypokalemia and increased hematocrit value were observed in animals of group A only. PRA was increased in about half of animals of group A, but it remained unchanged or rather reduced in animals of group B. Acute vascular lesions were defined as fibrinoid necrosis of the small arteries and arterioles, insudation of carbon particles into the arterial wall, or lesions resembling periarteritis. The vascular lesions were found in 19 (57.6%) of 33 animals of gloup A and in 17 (51.5%) of 33 animals of group B. There was no difference in incidence and histological features of the vascular lesions between the two groups. The presence or absence of the vascular lesions did not depend upon the level of blood pressure in both groups. Within the group A, there was no significant correlation between PRA and development of the vascular lesions.II. Long-term experiment.Twenty animals of two-kidney hypertension (Group A) and twenty-one of one-kidney hypertension (Group B) were observed for twenty weeks after the renal artery costriction. Hypertension developed similarly in both groups. In animals of group A, increased PRA, hypokalemia and increased hematocrit values were seen. But in animals of group B, PRA was not increased.Eight (38%) out of twenty-one animals of group B died, and all these eight animals had cerebral haemorrhage. None of group A animals died. Histologically fibrinoid necrosis was seen in all animals that died and had cerebral heamorrhage, but in another animals it was seen in only one of group A animals. Another chronic vascular lesions were seen frequently in both groups. There was no significant difference in blood pressure and in another parameters between animals that died and survived.It is concluded that the vascular lesions and cerebral haemorrhage can develop independently of PRA or level of blood pressure.