Two-kidney Goldblatt Hypertension Research Articles

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.

Micro-canaliculi in juxtaglomerular cells of two-kidney Goldblatt hypertensive rats

Juxtaglomerular (JG) cells in two-kidney Goldblatt hypertensive (2KGH) rats were examined ultrastructurally. In JG cells of the clipped kidneys of 2KGH rats, micro-canaliculi branched off from channel-like invaginations of plasma membrane and connected with the secretory renin granules. These findings suggest that micro-canaliculi may play important role in renin secretion from JG cells in 2KGH rats.

Modulation of renin-angiotensin and kallikrein gene expression in experimental hypertension.

Previous studies have shown that chronic low-dose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin II-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.

急性期の二腎性Goldblatt型高血圧ラットおよび高血圧自然発症ラットに及ぼすカプトプリルの影響

Effects of continuous oral administration of captopril were investigated on acute phase in two-kidney Goldblatt hypertensive (2 KGH) rats and spontaneously hypertensive rats (SHR). Systolic blood pressure gradually rose throughout the experimental period of 7, 14, 21 and 28 days in both 2 KGH rats and SHR. These gradual increases of systolic blood pressure were reduced by administration of captopril in both rats. Plasma renin activity were markedly increased throughout the experimental period in both rats treated with captopril, and were modestly increased in 2 KGH rats. In contrast, those changes in plasma renin activity were not obvious in SHR. In 2 KGH rats, juxtaglomerular index (JGI) and juxtaglomerular cell count (JGCC) of the clipped kidneys increased whereas JGI of the opposite kidneys decreased. In contrast, those changes in JGI and JGCC were not obvius in SHR. On the other hand, JGI and JGCC of the clipped kidneys increased in 2 KGH rats treated with captopril and those of the both kidneys increased in SHR treated with captopril. These results suggested that juxtaglomerular cells were related to the development of hypertension in 2 KGH rats, but were not clear in SHR. And these results were found that captopril showed antihypertensive effects, in spite of rises in JGI and JGCC of both 2 KGH rats and SHR.

Glomerular dynamics and salt balance in pregnant rats with renal hypertension.

These studies were aimed at investigating whether chronic hypertension in pregnancy causes changes both in salt excretion (NaE) and in glomerular hemodynamics. Metabolic and renal micropuncture studies were performed in pregnant (P) and Virgin (V) Munich-Wistar rats with normal blood pressure (N) and two-kidney Goldblatt hypertension (H). Mean NaE was higher in PN than VN (2.7 vs. 1.7 meq/day, P less than 0.01). Hypertension raised NaE both in P and V rats: in P and V rats with "benign" hypertension (blood pressure less than 180 mmHg) NaE averaged 3.2 and 2.6 meq/day, respectively (P less than 0.05); mean NaE was 5.9 and 3.8 meq/day, respectively (P less than 0.01), in P and V rats with "malignant" hypertension (blood pressure greater than or equal to 180 mmHg). Afferent arteriole resistance (Ra) averaged 1.73 and 3.50 10 dyn.s-1.cm5 in PN and VN, respectively (P less than 0.01). Hypertension raised Ra in V, but not in P rats (4.47 vs. 2.14 10 dyn.s-1.cm5, P less than 0.01). Thus glomerular plasma flow, glomerular capillary hydrostatic pressure, and single-nephron glomerular filtration rate were markedly higher in PH than VH rats: in PH rats single-nephron filtration fraction was significantly lower than in VH. These results show that in PH rats a marked rise in NaE is associated with glomerular vasodilation.

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.

Partition of carotid baroreceptor response in two-kidney renal hypertensive dogs.

This study evaluated the mechanism of carotid sinus baroreceptor resetting in two-kidney one-clip Goldblatt hypertension in dogs by partitioning the resetting between carotid sinus wall compliance and receptor neural elements. With dogs under halothane anesthesia, the left renal artery was constricted 70-80% with a Goldblatt clamp without disturbing the contralateral kidney. Ten weeks later, when mean blood pressure had risen to 151 +/- 6 mmHg (means +/- SE) compared with 105 +/- 5 mmHg in controls, we measured simultaneously whole nerve action potentials (N) and carotid sinus volume (V) during step changes in intrasinus pressure (P). Hypertensive N vs. P relationship was sigmoid shaped and shifted toward the P-axis compared with controls. Hypertensive V vs. P relationship was not significantly different from controls. The hypertensive N vs. V relationship derived from the composite plots of N vs. P and V vs. P was sigmoid shaped and shifted toward the V-axis compared with controls. These results suggest that the resetting of baroreceptors is due to changes in receptor properties rather than carotid sinus wall compliance.

Morphometric analysis of collagen network and plasma perfused capillary bed in the myocardium of rats during evolution of cardiac hypertrophy

In order to investigate the consequences of different types of cardiac hypertrophy on myocardial capillary and fibrosis density in rats we describe here, in the same hearts, the pattern of capillary bed density visualized by fluorescein isothiocyanate dextran (FITC-dextran) and the pattern of fibrosis density as determined by automated image analysis. Pressure overload was induced by clipping one renal artery in rats (one-clip, two-kidney Goldblatt hypertension, RHV). Volume overload was induced by creation of an arteriovenous shunt between the abdominal aorta and the vena cava (aorto-caval fistula model ACF). Animals were sacrified at 1, 3 and 6 months following surgical procedure. Immediately prior to sacrifice, FITC-dextran (MW 150,000) was injected with the animal under ether anesthesia. Five minutes later, cardiac diastolic arrest was induced by the i.v. injection of potassium chloride. The heart was rapidly excised and placed in a formaldehyde solution. The degree of cardiac hypertrophy was calculated after measurement of cardiac weight. Left ventricular wall thickness and cavity area were measured by microscopic methods. Capillary density and geometry were determined by morphometric methods, under ultraviolet light microscopy, using a graphic tablet connected to a microcomputer. The degree of myocardial fibrosis, visualized with Sirius Red, was estimated by the use of automated image analysis using light microscopy. In renovascular hypertension, cardiac hypertrophy was maximum at one month (36%) and persisted through the six months of the study. This increase in cardiac mass was concentric, due to a significant increase in ventricular wall thickness and was associated with a marked increase in fibrosis and a significant decrease in subendocardial capillary density. These effects existed already one month and did not change with time. In the aorto-caval fistula model, cardiac hypertrophy was also maximum at one month (+56%), but this eccentric increase in cardiac mass was associated with no significant change in left ventricular wall thickness, but rather with a significant increase in the surface area of the left ventricular cavity. This volume overload hypertrophy was associated with a decrease in subendocardial capillary density which was negatively correlated with time. In contrast to concentric hypertrophy there was no increase in the fibrosis density compared to the sham-operated groups. Despite the identical degrees of hypertrophy, pressure and volume cardiac overload differed in a significant manner in both left ventricular wall thickness and cavity surface area.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of vasopressin blockade on blood pressure in conscious rats with malignant two-kidney Goldblatt hypertension.

The role of vasopressin (VP) in maintaining blood pressure in malignant two-kidney one-clip Goldblatt hypertension in chronically catheterized conscious rats was investigated by studying the effect of two structurally different VP pressor antagonists. Injections of either 20 micrograms/kg of dPTyr(Me)AVP or 10 micrograms/kg of d(CH2)5Tyr(Me)AVP failed to alter mean arterial pressure or heart rate, although both antagonists completely inhibited the pressor response elicited by exogenous VP. These results suggest, that VP is not involved as a pressor hormone in the maintenance of high blood pressure in this type of experimental hypertension.

The angiotensin II pressor system of the rat forebrain.

An anterior hypothalamic knife cut that leaves intact two central sites of action of angiotension II produces the same deficits in the pressor responses to angiotensin II that have been attributed to destruction of two circumventricular organs (the subfornical organ and the organum vasculosum of the lamina terminalis). The central pressor actions of angiotensin II are necessary for the full expression of renin-dependent renal hypertension. The anterior hypothalamic knife cut attenuates renin-dependent aortic ligation hypertension. It has been shown that electrolytic destruction more anterior to this knife cut, in the anteroventral 3rd ventricle region, also attenuates two forms of renin-dependent hypertension, aortic ligation hypertension and two-kidney Goldblatt hypertension in the rat. Electrolytic lesions in the subfornical organ also reduce renin-dependent, two-kidney Goldblatt hypertension. These data are consistent with the hypothesis that a common efferent system from the organum vasculosum of the lamina terminalis and subfornical organ mediates the central pressor response to angiotensin II and is involved in the development of renin-dependent hypertension. A model is proposed for the circuitry in the rat forebrain that is involved in the pressor response to angiotensin II.

Central and peripheral catecholamine synthesizing enzymes during the development of two-kidney, one clip hypertension in rats.

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-beta-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (+49.0%, P less than 0.001 and +36.6%, P less than 0.001, respectively) and DBH activity was also increased in the superior cervical ganglia (+22.8%, P less than 0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.

Relative contribution of vasopressin and angiotensin II to the altered renal microcirculatory dynamics in two-kidney Goldblatt hypertension.

The renal microcirculation was assessed in non-clipped kidneys of 23 Munich-Wistar rats with two-kidney one-clip Goldblatt hypertension. Four weeks after placement of a renal arterial clip, mean systemic arterial pressure averaged 163 +/- 5 mm Hg in hypertensive rats as compared to 108 +/- 2 in sham-operated controls (n = 6 rats). Non-clipped kidneys in hypertensive rats were characterized by higher glomerular capillary hydraulic pressures, single nephron glomerular filtration rate, and afferent arteriolar resistance. The glomerular capillary ultrafiltration coefficient was significantly reduced in hypertensive rats. In 10 of these rats, intravenous infusion of the angiotensin antagonist, saralasin, or the converting enzyme inhibitor, SQ20881, led to significant reductions in systemic arterial pressure and in afferent and efferent arteriolar resistance, on average by 8 +/- 3%, 15 +/- 4%, 28 +/- 5%, respectively. These changes were associated with significant increase in glomerular plasma flow, while ultrafiltration coefficient remained unaffected. In the presence of saralasin or SQ20881, infusion of a specific antagonist of the vascular action of arginine vasopressin led to significant systemic but not renal vasodilation. Thus, whereas systemic arterial pressure fell further, on average by 23 +/- 2%, renal arteriolar resistance remained constant, resulting in marked reduction in glomerular capillary hydraulic pressures (by 18 +/- 2%) and glomerular plasma flow rate (by 28 +/- 10%). Because of these pronounced reductions in glomerular pressures and flows induced by vasopressin antagonist, single nephron glomerular filtration rate fell markedly in hypertensive rats (by 34 +/- 6%) despite normalization of ultrafiltration coefficient. When hypertensive rats (n = 7) were treated with vasopressin antagonist alone, a modest fall in systemic arterial pressure was again observed in the absence of changes in renal arteriolar resistance. Due to this selective extrarenal vasodilatory action of vasopressin antagonist, glomerular capillary hydraulic pressure, plasma flow rate, and single nephron glomerular filtration rate again fell markedly. When these vasopressin antagonist pre-treated hypertensive rats were given saralasin or SQ20881, marked reductions in renal arteriolar resistance were observed in association with a significant increase in glomerular plasma flow rate. These observations made during acute inhibition of angiotensin II and vasopressin indicate that both of these vasopressin hormones may play important roles in maintaining systemic hypertension in hypertensive rat. By virtue of its preferential constrictor effects on extrarenal rather than renal vasculature vasopressin serves to maintain high glomerular pressures and flows in the non-clipped kidney of Goldblatt hypertensive rats.

Effect of anteroventral third ventricle lesions on vascular sodium-pump activity in two-kidney Goldblatt hypertension.

We studied the effects of anteroventral third ventricle (AV3V) lesions on the vascular Na+-pump activity and blood pressure of rats prepared by the two-kidney Goldblatt procedure. Blood pressures and Na+-pump activity of the isolated tail arteries, measured as ouabain-sensitive 86Rb+-uptake were determined in rats with renal artery clips, rats with AV3V lesions, and rats with AV3V lesions. Rats with renal artery clips developed higher blood pressures (40%) and higher vascular Na+-pump activity (20%-35%) than rats with no renal clips. Placement of AV3V lesions prior to the placement of renal clips prevented the increase in blood pressure and the increase in vascular Na+-pump activity. Plasma potassium and creatinine concentrations, nonspecific 86Rb+-uptake, and hematocrit were not different among these groups. Plasma sodium concentration was elevated in the AV3V lesioned control group. These experiments suggest a possible role of this CNS region in the regulation of vascular Na+-pump function during hypertensive states.

Effect of castration and testosterone substitution on the urinary output of gamma-glutamyl transpeptidase and of N-acetyl-beta-D-glucosaminidase of male rats with renovascular hypertension.

The effect of castration of male rats with experimental renal hypertension ('two-kidney Goldblatt hypertension') was studied on the height of the hypertension and on the urinary output of gamma-glutamyl transpeptidase (gamma GT) and of N-acetyl-beta-D-glucosaminidase (NAG). Castration was carried out immediately after clamping one renal artery. Some of the castrates received testosterone substitution from the 3rd postoperative week onwards. Uncastrated hypertensive males served as controls. The experiments were carried out 8-18 weeks after eliciting high blood pressure. Hypertension as well as enzymuria were less expressed in castrates than in uncastrated males or in testosterone-substituted rats. In all animals studied the gamma GT excretion rate showed a positive correlation with the blood pressure. The output of gamma GT and of NAG as well as the specific gamma GT activity of the renal membrane fraction was lower in castrates than in uncastrated males or in substituted castrates. In uncastrated males and in testosterone-substituted castrates the daily NAG output showed a direct correlation with the renal hydroxyproline content. No such correlation was found in castrated males. The kidneys of castrates and of testosterone-substituted castrates contained less hydroxyproline than those of uncastrated males.

Norepinephrine turnover in the cardiovascular tissues and brain stem of the rabbit during development of one-kidney and two-kidney Goldblatt hypertension.

To assess the role of the sympathetic and central noradrenergic neurons in one- and two- kidney Goldblatt hypertension, we examined the concentration and turnover of norepinephrine (NE) in the aorta, mesenteric artery, left ventricle, hypothalamus, midbrain, and pons medulla of hypertensive and control rabbits. Animals were made hypertensive by constriction of the left renal artery after right nephrectomy (1KGH group) or with the right kidney left intact (2KGH group), or were sham-operated on the renal artery (1KGC and 2KGC groups). At 14 days after the constriction, the blood pressure was increased to 136 +/- 3 mm Hg in the 1KGH vs 98 +/- 3 mm Hg in the 1KGC (p less than 0.001), and 136 +/- 2 mm Hg in the 2KGH vs 94 +/- 2 mm Hg in the 2KGC group (p less than 0.001). Turnover time in the aorta, mesenteric artery, and left ventricle in the 1KGH group was decreased to 47%, 45%, and 65% of that in the 1KGC group, respectively. Results suggest that enhanced sympathetic neuron activity in the cardiovascular system, especially in the arteries, contributes to the development of one-kidney Goldblatt hypertension. Norepinephrine turnover in the cardiovascular tissues in the 2KGH group and in the brain stem in the 1KGH and 2KGH group was not different from that in the control group.

Changes in arterial wall properties during development and maintenance of renal hypertension.

Segments of carotid and tail arteries were used to determine the effects of two-kidney Goldblatt hypertension on mechanical properties and chemical contents. Arteries were obtained after 4 and 12 wk of hypertension. Systolic pressures averaged 129 mmHg in control animals and 150 mmHg in hypertensive ones. Pressure-diameter data were recorded under conditions of active (145 mM K+) and passive (0 Ca2+ and 2 mM EGTA) smooth muscle. Small increases in passive stiffness were found after 4 and 12 wk in the carotid arteries of hypertensive animals, but no significant change occurred in the tail arteries. Small but significant decreases in total connective tissue content of these arteries were found after 12 wk of hypertension. Maximum values of active stress response were significantly larger in carotid arteries from hypertensive animals at both 4 and 12 wk of hypertension. No significant differences were found for the tail arteries. The K+ content of the carotid but not the tail artery was larger for the hypertensive animals. When corrected for differences in relative cell content most of the differences in active force development were eliminated. The differences in passive mechanics can not be explained on the basis of the changes in connective tissue content. The active smooth muscle responses and content changes suggest that they are directly related to the moderate elevation of arterial pressure.

Different effects of captopril on blood pressure in the acute and chronic two-kidney Goldblatt hypertensive dogs.

Captopril was administered to acute (8 to 14 days after unilateral renal artery constriction) and chronic (71 to 127 days after the constriction) two-kidney Goldblatt hypertensive dogs, and to normotensive ones for 21 days (oral administration of 10, 20 and 40 mg/kg/day, consecutively each 7-day period). The decrease of arterial blood pressure was remarkable in hypertensive animals with high plasma renin activity, but not in the normotensive animals. In the acute stage of hypertension, the antihypertensive effect of captopril was dose-dependent and persistent even after its cessation. In the chronic stage of hypertension, blood pressure also decreased, but the response was not dose-dependent and did not continue after cessation. Plasma renin activity rose in both hypertensive and normotensive animals during the treatment with captopril. There were no significant changes in heart rate, daily urinary volume, sodium balance, and renal clearances of sodium (CNa), potassium (CK), chloride (CCl) and creatinine (CCr). Circulating blood volume was also not altered. These results indicate that the main mechanism of antihypertensive effect of captopril in two-kidney Goldblatt hypertensive dogs is an inhibition of the angiotensin converting enzyme. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanism(s) of maintaining blood pressure between the two stages of two-kidney Goldblatt hypertension in dogs.

Evidence of early structural change in the artery wall of two-kidney one-clip Goldblatt hypertensive rats.

Vascular structural changes were studied during the development of two-kidney one-clip renal hypertension. The weight of the arteries and the concentration and total amount of ribonucleic acid, deoxyribonucleic acid, alkali-soluble proteins, collagen and elastin of the vascular wall were measured. Tritiated thymidine uptake was also determined 15 and 30 days after clipping. Hypertension developed in 58% of the animals while the rest remained normotensive. A significant increase in artery weight and in the total amount of nucleic acids and proteins was found in hypertensive rats. The uptake of 3H thymidine by the arteries of hypertensive rats was significantly increased 15 days after clipping. This increment showed a significant correlation with blood pressure levels. Present data seem to indicate that the increase in vessel wall dimensions observed is partly due to an increase in the number of smooth muscle cells during the acute phase; this alteration appears to be mainly due to the rise in blood pressure.

Properties of intestinal and cutaneous arteries and veins in two-kidney one-clip Goldblatt hypertension.

This study evaluates whether changes in arterial and venous smooth muscle contractility and extensibility precede or result from the elevated arterial pressure (MAP) and total peripheral resistance (TPR) of two-kidney one-clip Goldblatt hypertension (2-KGH). The experiments measure the contractile and extensibility properties of rings of canine mesenteric, cutaneous, gracilis, and pulmonary arteries and veins (0.4-1.0 mm OD) prior to and days 1 and 32 after the initiation of two-kidney one-clip Goldblatt hypertension (2-KGH), produced by unilateral constriction of the renal artery (URAC). The reactivity (ED50) and tension development to norepinephrine (NE), angiotensin II (ANG II), potassium chloride (KCl), serotonin (5-HT), 9 alpha, 11 alpha-epoxymethano prostaglandin H2 (EMP), prostaglandin B2 (PGB2), and CaCl2 were determined. Mean arterial pressure (MAP) and TPR were unchanged from pre-URAC values 24 h post-URAC but were significantly elevated 32 days post-URAC. The ED50's for 5-HT, ANG II, EMP, and PGB2 were decreased in each of the arteries and veins obtained from dogs with 2-KGH, within 24 h post-URAC, and either became more pronounced (PGB2, EMP, and 5-HT) or returned to pre-URAC values by day 32 post-URAC. The ED50's for NE, KCl, and CaCl2 were unchanged from pre-URAC values. Maximal tension development of the arteries and veins to each of the agonists increased within 24 h post-URAC, prior to an increase in MAP or TRP. Within 32 days post-URAC, maximal tension development of the veins obtained from 2-KGH was increased from pre-URAC values, whereas tension development by the arteries was decreased. Extensibility decreased in each of the arteries and veins obtained from dogs with 2-KGH 24 h post-URAC. The extensibility decreased further by day 32 post-URAC as the level of MAP and TPR increased. These data support the postulate that altered venous and arterial smooth muscle contractility and extensibility precede the elevated MAP and TPR of 2-KGH in dogs. Moreover, since these changes occur in both artery and vein, they must reflect the action of circulating humoral or intrinsic vascular or neural substances. Finally, the decrease in arterial contractility suggests that the enhanced vascular responses in vivo and in situ may reflect the greater mechanical advantage of the hypertrophied blood vessel and not an arterial vasculature with enhanced contractility.

Renal blood flow changes in contralateral kidney of Goldblatt hypertensive dog.

Sequential changes in systemic arterial blood pressure (BP), renal blood flow (RBF) in the contralateral kidney, and plasma renin activity (PRA) were examined on conscious dogs with construction of a single renal artery (RAC). An increase of 24 mmHg in bP occurred within 2 days after RAC, and BP later plateaued at a lower level. RBF in the contralateral kidney transiently increased by 24% and then returned to the control level in 11-14 days. PRA also peaked early after RAC and then returned to control. The clamp was tightened and the renal artery was occluded (RAO) 3-20 days after RAC. BP, RBF, and PRA increased to an even greater degree than after RAC. BP peaked at 145 mmHg, and RBF increased 61.5% at 2-3 days after RAO. BP and RBF both decreased but remained above the control for the duration of the study, BP at 127 mmHg and RBF at 256 ml/min. RBF per gram for the hypertrophied contralateral kidney was calculated from the RBF before death and the weight at death. The final RBF per gram of the contralateral kidney (2.7 ml.min-1.g-1) decreased and renal vascular resistance increased compared with the estimated control RBF/g (3.7 ml.min-1.g-1) and renal vascular resistance. These results suggest that the final RBF of the contralateral kidney is not increased in proportion to its increase in weight and that it may be relatively hypoperfused in two-kidney one-clip Goldblatt hypertension.