Experimental Renal Hypertension Research Articles

Flax lignan concentrate reverses alterations in blood pressure, left ventricular functions, lipid profile and antioxidant status in DOCA-salt induced renal hypertension in rats

Context Earlier we reported cardioprotective, antihyperlipidemic, and in vitro antioxidant activity of flax lignan concentrate (FLC) obtained from the seeds of Linum usitatissimum L. (Linaceae).Objective To investigate the effect of FLC in deoxycorticosterone acetate (DOCA)-salt induced experimental renal hypertension in rats. Materials and methods Hypertension was induced in uninephrectomized (UNTZD) male Wistar rats (230–280 g) by injecting DOCA (25 mg/kg, subcutaneously, twice weekly) and supplementing 1% NaCl in drinking water for 5 weeks. The rats were divided in six groups. Captopril (30 mg/kg, p.o.) and FLC (200, 400 and 800 mg/kg, p.o.) were administered daily to the rats of groups III–VI, respectively, for 5 weeks. Various hemodynamic and biochemical parameters were investigated as well as histology of kidney and heart were carried out. Results In this study, the FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) decreased the systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure. It also significantly (p < 0.01, p < 0.001) decreased elevated end diastolic pressure (EDP), dP/dt max and dP/dt min, organs weights (kidney and heart) and activities of hepatic, renal and cardiac marker enzymes in the serum. Furthermore, FLC (400 and 800 mg/kg) significantly (p < 0.01, p < 0.001) restored altered antioxidant status, serum electrolyte level, lipid profile values, and histological abnormalities. Captopril (30 mg/kg) showed maximum antihypertensive effect but low dose of FLC (200 mg/kg) was not enough to show the antihypertensive activity. Conclusion FLC possessed antihypertensive effect via modulation of endogenous enzymes in DOCA-salt induced renal hypertension in rats.

Pharmacology of (+)-, (+)-and (-)-2:2-diphenyl-3-methyl-4-morpholino-butyrylpyrrolidine.

Abstract (±)-2:2-Diphenyl-3-methyl-4-morpholino-butyrylpyrrolidine (R610) is a more active analgesic agent in mice, rats and guinea pigs than morphine. The analgesic activity is due to the (+)-isomer (R875). The (–)-isomer (R898) is nearly inactive. R610 lowers the body temperature to below control levels in immobilised rats, inhibits the respiration in unnarcotised rats, lowers the blood pressure in unnarcotised rats with experimental renal hypertension, and causes mydriasis in mice. It also augments the action of barbiturates in mice. In all these respects the (+)-isomer is the active compound of the racemic mixture. The (–)-isomer is almost as toxic as the (+)-isomer, which has a broader therapeutic margin than the (±)-form. The dosage-toxicity relation of highly active analgesic agents in mice and rats is irregular especially in the lower dosage range.

Blood pressure-independent effects of enhanced NO/cGMP signalling and gender on aortic remodelling in experimental renal hypertension

Results SNX led to increases in systolic blood pressure, with lower levels in F rats (F-SNX 129 ± 13 mmHg vs. M-SNX 140 ± 11 mmHg). Bay 41-8543 and hydralazine reduced blood pressure to control levels. Aortic remodelling was characterized by marked media thickening in both SNX groups, with a more pronounced increase in M versus F (127 ± 9 vs. 108 ± 6% of control; p < 0.001). Intima-media ratio was reduced in both uremic groups, with significant sex differences (M-SNX 66 ± 7% vs. F-SNX 80 ± 8% of control; p < 0.01). Furthermore, gender differences were observed in media-to-lumen ratio as indicator of aortic hypertrophy. The ratio was significantly higher in SNX males only (M-SNX 131 ± 9% vs. F-SNX 107 ± 15% of control; p < 0.001). Bay 41-8543 significantly ameliorated media thickness (111 ± 10 vs. 127 ± 9% of control in M; 101 ± 7 vs. 108 ± 6% of control in F; p < 0.05), intima-media ratio (85 ± 10 vs. 66 ± 7% of control in M; 91 ± 6 vs. 80 ± 8% of control in F, p < 0.01) and media-to-lumen ratio (107 ± 9 vs. 131 ± 9% of control in M; p < 0.001). Despite a similar reduction in blood pressure, hydralazine treatment did not alter aortic wall remodelling. These morphological changes were accompanied by elevated collagen I and reduced elastin protein expression at the level of aortic media, with decreased elastin/collagen ratio in untreated SNX groups, as marker of aortic wall stiffening. Bay 41-8543 treatment successfully prevented these molecular alterations (collagen I protein expression: 9.4 ± 0.3 vs. 14.5 ± 1.1% in females and 9.6 ± 0.4 vs. 16.1 ± 1.0% in males), while hydralazine showed no effects. SNX was characterized by increased extracellular matrix turnover with up-regulation of MMP2 and TIMP1 genes, more pronounced in males than in females (M-SNX 1.8 ± 0.1 vs. F-SNX 1.1 ± 0.1 for MMP2; M-SNX 4.2 ± 0.8 vs. F-SNX 2.7 ± 0.6 for TIMP1; both expressed as relative values vs. controls). In the male Bay 41-8543-treated group, expression of these genes was significantly lower (1.4 ± 0.1 MMP2from 4th International Conference of cGMP Generators, Effectors and Therapeutic Implications Regensburg, Germany. 19–21 June 2009

Is Renal Artery Stenting the Correct Treatmentof Renal Artery Stenosis?

The case favoring renal artery stenting for individuals with renal artery hypertension is largely circumstantial. At best, the clinical evidence presented in this discussion is derived primarily from nonrandomized cohort studies. It would certainly be easier to argue that medical therapy is preferred for such individuals because there are 3 published randomized clinical trials that concluded just that and none that support renal artery intervention. Nonetheless, there is considerable evidence to support the role for revascularization in general, and stenting specifically, as an important adjunctive therapy to medical therapy in the care of patients with renal artery stenosis (RAS). The argument has 3 principal components: observations about the impact on cardiovascular physiology, end-organ effects, and natural history. Response by Dworkin and Jamerson p 270 RAS is associated with and is an important cause of secondary hypertension. RAS causes endocrine activation with release of renin from renal juxtaglomerular cells. Renin catalyzes the breakdown of angiotensinogen to angiotensin I. Angiotensin I is transformed by angiotensin-converting enzyme into angiotensin II, and angiotensin II promotes the release of aldosterone from the adrenal cortex.1 Angiotensin II is a potent vasoconstrictor,2 substantially more potent than epinephrine, and is implicated in end-organ damage in the heart3 and kidney.4 RAS is suggested to cause 2 types of hypertension. With unilateral RAS and a normally perfused and normally functioning contralateral kidney, blood pressure elevation is referred to as “renin dependent” and is characterized by increased peripheral resistance.5,6 In this circumstance, renin and angiotensin levels remain elevated, but volume expansion is limited by natriuresis of the contralateral normally functioning kidney.6 Importantly, although renin levels are elevated, the value of peripheral or even renal vein renin values is limited by substantial overlap with patients having essential hypertension.7,8 When stenoses are bilateral or when the …

Factors influencing acute ischaemia-induced renal hypertension in rats.

To verify if the acute hypertension that occurs after reversal of complete renal ischaemia is related to the duration of ischaemia, is different in one-kidney (1K) and two-kidney (2K) rats, and is prevented by angiotensin receptor blockade. Four groups of Sprague-Dawley rats anaesthetized with pentobarbitone were studied before, during and after a reversible, complete renal ischaemia achieved by functional right nephrectomy. In 1K rats (group 1, n = 21), reopening of right renal hilum after functional right nephrectomy of 180, 60 and 30 min was followed by peak increases in systolic blood pressure of 76.0 10.1 mmHg, 36.5 10.0 mmHg and 18.4 4.4 mmHg, respectively (mean SEM). In 2K rats (group 2, n = 21), functional right nephrectomy of 180, 60 and 30 min was followed by smaller increases in blood pressure of 49.8 7.6 mmHg, 5.9 3.3 mmHg and 8.3 2.1 mmHg, respectively. Plasma renin activity was directly related to the duration of functional right nephrectomy, and was greater in 1K rats. In group 3, irbesartan administered to 1K rats (n = 8) during functional right nephrectomy almost completely prevented the development of hypertension upon reopening. In group 4, labetalol injected intravenously in 1K rats (n = 3) did not prevent the blood pressure surge at reopening (49.2 8.5 mmHg). An experimental acute renal hypertension may be elicited both in 1K and in 2K rats and for functional right nephrectomy of 30, 60 and 180 min duration. The increase in blood pressure is proportional to the duration of functional right nephrectomy and greater in 1K than in 2K rats. The experimental acute renal hypertension is due to acute release of renin and generation of endogenous angiotensin II, and is specifically prevented by the angiotensin II type 1 receptor blocker, irbesartan, but not by labetalol.

The effects of experimental acute renal hypertension on sympathetic nerve activity to the kidney in the rat

The reopening of the renal hilum after a period of complete renal ischaemia is followed by a hypertensive crisis (the experimental acute renal hypertension: EARH) which is due to the acute release of renin and endogenous angiotensin II formation. The present study was done to verify if the EARH is accompanied by simultaneous alterations in efferent sympathetic nerve activity to the kidney. The experiments were done on Sprague-Dawley spontaneously breathing rats (200-300 g) anaesthetized with nembutal (n=5). After excision of the left kidney, the renal nerves to the right kidney were exposed by a retroperitoneal approach and a single nerve strand was positioned on a bipolar hook electrode to record renal sympathetic postaganglionic nerve activity (RSNA). Threads were placed around the right renal artery and vein in order to produce a complete renal ischaemia. After three hours these ties could be loosened to reestablish blood flow to and from the kidney (functional right nephrectomy: FRN). RSNA, blood pressure, heart rate, rate of breathing and rectal temperature were continuously recorded. From the beginning of the experiment (time 0) to its end (time 300 min) the nerve strands were left untouched and their position on the electrode was unchanged. As previously reported with respect to control conditions RSNA decreased during three hours of FRN from 39.1 ±3 imp/sec at baseline, to 13.7 ±3 at the end of three hours of FRN period (Recordati, J Hypertens, 18: 1277, 2000). The present report describes what occurred at the reopening of the right renal hilum when a hypertensive crisis and tachycardia are observed. In four out of five rats this hypertension was accompanied by a 1-3 min continuous firing of the RSNA to a mean peak increase of 28.7 ±7 imp/sec at a time the mean systolic blood pressure had increased to 209.4 ±21 mmHg. RSNA subsequently recovered towards a spontaneous normal bursting discharge, while blood pressure persisted elevated. These results indicate that the increase in sympathetic activity at the reopening of the renal hilum is short-lasting and therefore may only be partially responsible for the observed persistent increase in blood pressure. The consistently observed excitation of RSNA may be due to a reflex excitatory effect upon stimulation of renal receptors or of nonrenal sympathetic afferents, or, more probably, from central and ganglionic excitation of sympathetic neurons by a substance released by the ischaemic kidney.

Sixtieth Anniversary of Angiotensin

The journal, very recently, paid tribute to the 100th anniversary of the discovery of renin by Tigerstedt and Bergman.1,2 Forty years later, 2 independent investigative groups in Buenos Aires and Indianapolis, headed by Drs Eduardo Braun-Menendez and Irvine H. Page, respectively, identified the active polypeptide angiotensin that explained the pressor effect of renal hypertension.3–6 Thus, using relatively unsophisticated methods (in terms of present day technology), the precise peptide that produced experimental renal hypertension was identified. In the accompanying online-only historical commentary, Drs Nidia Basso and …

An experimental acute angiotensin-mediated renal hypertension in the rat

An experimental acute angiotensin-mediated renal hypertension in the rat

Isolated diastolic dysfunction is coupled to reduced phosphotransfer enzyme activity in experimental renal hypertension Chari Y. T. Hart, Petras P. Dzeja, Andre Terzic, Margaret M. Redfield. Mayo Clinic, Rochester, MN

Isolated diastolic dysfunction is coupled to reduced phosphotransfer enzyme activity in experimental renal hypertension Chari Y. T. Hart, Petras P. Dzeja, Andre Terzic, Margaret M. Redfield. Mayo Clinic, Rochester, MN

Differential expression of glial fibrillary acidic protein (GFAP) in the retinae and visual cortices of rats with experimental renal hypertension

To examine the expression of the GFAP protein in the retina and visual cortex under normal and pathological conditions, hypertension was induced in adult male Sprague-Dawley rats by applying silver clips onto renal arteries and the change in GFAP expression was followed by Western blotting and immunocytochemical staining. One week after operation when the induced hypertension was at the initial stage, GFAP expression in the retina was reduced to half of the sham control. By 4 weeks, when consistent hypertension was developed, a further decrease in the level of GFAP expression in the retina to one third of the sham control was observed. Immunocytochemical staining showed that the number of GFAP-positive cells in the nerve fiber layer of the retina of the hypertensive rat was reduced to less than one third of the sham control. However, similar changes in GFAP expression in the visual cortex of hypertensive rats were not observed. This study represents the first report to date on GFAP expression in the retina and visual cortex and includes discussion of the possible mechanisms through which GFAP expression is mediated.

Role of endogenous endothelin-1 in experimental renal hypertension in dogs.

Endothelin-1, a vasoconstrictive peptide released by endothelium, may be involved in the pathophysiology of hypertension. The goal of the present study was to evaluate the role of endogenous endothelin-1 in renal hypertension in dogs. The model of hypertension consisted of silk tissue wrapping of the left kidney, which produced hypertension associated with perinephritis after 6 to 8 weeks. Thirty-two anesthetized open chest dogs were studied randomly: 8 dogs with perinephritic hypertension received the nonpeptidic ETA-ETB receptor antagonist bosentan (group 1); 8 other hypertensive dogs received the vehicle solution (group 2); 8 healthy dogs received bosentan (group 3); and 8 healthy dogs received the vehicle solution (group 4). Bosentan was injected as an intravenous bolus (3 mg/kg) followed by a 1-hour infusion at a rate of 7 mg.kg-1.h-1. In hypertensive dogs, bosentan produced a similar decrease (P = .0001) of both left ventricular systolic and mean aortic pressures, which averaged 38 mm Hg (-22% and -24%, respectively). These parameters remained unchanged with the vehicle solution. Left ventricular end-diastolic and left atrial pressures also declined significantly with bosentan (P = .0005 and P < .05, respectively). Left ventricular lengths tended to decrease. The other cardiovascular parameters (heart rate, peak [+]dP/dt, time constant of relaxation, and coronary vascular resistance) did not change significantly. In healthy dogs, bosentan decreased mean aortic pressure by 19 mm Hg (P = .004). Vehicle solution had no effect. Plasma endothelin-1 levels, similar under basal conditions in healthy and hypertensive dogs, increased 30-fold with bosentan (P = .0001). Specific endothelin-1 receptor antagonism markedly lowers blood pressure in experimental hypertension but is less effective on blood pressure of healthy animals. This suggests that endothelin-1 plays a role in the pathophysiology of hypertension but contributes to a lesser extent to the maintenance of normal blood pressure. This role of endothelin-1 is unrelated to its plasma levels. The increase of plasma endothelin-1 with bosentan, due either to a displacement of endothelin-1 from its receptor or to a feedback mechanism, does not prevent this blood pressure reduction.

Role of bradykinin in the antihypertensive and cardioprotective actions of converting enzyme inhibitors.

Angiotensin converting enzyme inhibitors (ACEIs) not only reduce angiotensin II synthesis but also potentiate endogenous kinins. In addition to their antihypertensive actions, accumulated evidence has demonstrated an improvement by ACEIs of cardiac function, cardiac structural and metabolic status, and myocardial blood flow in conditions such as cardiac ischemia, left ventricular hypertrophy, and myocardial infarction. The mechanisms underlying the antihypertensive and cardioprotective actions of ACEIs are under intensive investigation. A reduction of angiotensin II synthesis is undoubtedly responsible for a major part of the antihypertensive effects of ACEIs. However, in experimental renal hypertension but not in genetic hypertension, bradykinin potentiation has been shown to partially mediate the acute and chronic antihypertensive actions of these drugs. In addition, experimental observations suggest that bradykinin potentiation plays a pivotal role in the cardioprotective effects of ACEIs.

Characteristics of arterial myosin in experimental renal hypertension in the dog.

We compared myosin samples isolated from iliac-femoral arteries of control and renal (stenosis) hypertensive dogs to determine the effects of increased blood pressure on the characteristics of the myosin. The ratio of 204-kd (SM-1) to 200-kd (SM-2) myosin heavy chains was approximately 1:0.75 for myosin from the iliac-femoral artery of normotensive dogs. This was not altered significantly in response to hypertension. Both SM-1 and SM-2 myosin heavy chains cross-reacted with antibody against smooth muscle myosin on Western blot analysis. In addition to these heavy chains, purified myosin from both groups showed a very faint protein band slightly below the 200-kd myosin heavy chain on electrophoresis on a highly porous sodium dodecyl sulfate-polyacrylamide gel. This protein band cross-reacted with antibody against nonmuscle myosin but not with smooth muscle myosin antibody. The 20- and 17-kd light chains of myosin isolated from normotensive and hypertensive dogs gave similar results on isoelectric focusing. Peptide maps of tryptic digests of heavy chains revealed both quantitative and qualitative differences. The Ca(2+)-activated myosin ATPase activity measured in high salt (0.5 mol/L KCl) was similar for myosin from both groups, whereas the potassium (ethylenedinitrilo)tetraacetic acid-stimulated ATPase of myosin from hypertensive animals was higher than that from normotensive animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Stevioside effect on renal function of normal and hypertensive rats

Physiological and pharmacological experiments have suggested that Stevioside from the leaves of Stevia rebaudiana acts as a typical systemic vasodilator. The effect of Stevioside on renal function in both normal and with experimental renal hypertension rats (GII) was evaluated using clearance techniques. Stevioside provoked hypotension, diuresis and natriuresis in both the normal and hypertensive rats. Normal rats presented an increase in renal plasma flow (RPF) and glomerular filtration rate (GFR) constant following Stevioside administration. The last effect is in part due to vasodilation of both the afferent and efferent arterioles. Moreover, Stevioside infusion in hypertensive rats caused an increase in RPF and GFR. These data are consistent with impairment of a renal autoregulation mechanism in this experimental hypertensive model.

Role of Bradykinin in Chronic Antihypertensive Actions of Ramipril in Different Hypertension Models

We investigated the chronic effect of bradykinin B2-receptor blockade on the antihypertensive actions of the angiotensin-converting enzyme (ACE) inhibitor ramipril in three different hypertensive rat models, the two-kidney/one-clip (2K1C) hypertensive Wistar rat, the kinin-deficient 2K1C hypertensive Brown Norway Katholieke (BN-K) rat, and the spontaneously hypertensive rat (SHR). Chronic blockade of bradykinin B2 receptors by subcutaneous infusion of the new bradykinin antagonist HOE 140 (500 micrograms/kg/day) attenuated the antihypertensive effect of ramipril only in 2K1C hypertensive Wistar rats, but not in 2K1C BN-K rats and SHR. Our data demonstrate for the first time that potentiation of endogenous kinins contributes to chronic antihypertensive actions of ACE inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.

Urinary 18,19-dihydroxycorticosterone and 18-hydroxy-19-norcorticosterone excretion in patients with primary and secondary aldosteronism

18,19-Dihydroxycorticosterone (18,19(OH) 2-B) and 18-hydroxy-1 9-norcorticosterone (18-OH-19-nor-B) measurements were carried out on the urine of patients with primary aldosteronism (PA), essential hypertension (EHT), and liver cirrhosis with (LC, SA ( + )) and without (LC, SA( − )) aldosteronism. The separation of these steroids was performed by extraction and high-performance liquid chromatography followed by radioimmunoassay (RIA) with specific antibodies prepared in our laboratory. 18, 19(OH) 2-B excretion was elevated in patients with PA (24 ± 5.9 [± SE] μg/24 hr; n = 15) and LC, SA ( + ) (83 ± 9.4 μg/24 hr; n = 8). Values in LC, SA (-) (3.1 ± 1.2 μg/24 hr; n = 8) and in EHT (3.7 ±0.4 μg/24 hr; n = 42) were found to be similar to those in normal subjects (5.5 ± 0.9 μg/24 hr; n = 30). The values of urinary 18-OH-19-nor-B in PA and LC, SA( + ) were higher than in LC, SA(−) EHT and normal subjects ( P < 0.05). Values in the latter three groups, as compared with each other, did not show significant alterations. Nothing is known about the biologic relevance of 18,19(OH) 2-B and very little about that of 18-OH-19-nor-B, but the latter steroid seems to potentiate experimental renal hypertension. One can speculate about possible roles of both steroids as precursors of other steroids, e.g., the biologically potent mineralocorticoid 19-noraldosterone. The data obtained suggest that it is not relevant to measure the urinary levels of either steroid in these clinical syndromes.

Changes in the hemostasis and fibrinolysis system in rats with experimental renal hypertension

The arterial renal hypertension (170-180 mm Hg compared to the norm 100-120 mm Hg) developed in 2 months after one side nephrectomy and partial occlusion of the other renal artery. The level of high molecular weight plasma proteins was raised which led to the increase in the peripheral vessel resistance and hypertension degree. Fibrinolysis was depressed in the blood and in the cortical zone of the kidney. In early stages of hypertension fibrinolysis was sharply elevated, and high molecular weight compounds content was decreased. The antithrombin III and nonenzymatic fibrinolysis level were increased during the whole period (10-150 days).

Renin inhibitors as possible antihypertensive agents.

The blockade of the renin-angiotensin system by inhibition of angiotensin-converting enzyme has become an established principle in the treatment of hypertension. This has stimulated interest in the inhibition of renin, the enzyme which catalyzes the first and rate-limiting step in the formation of angiotensin II. During recent years, considerable progress has been made in the development of renin inhibitors. Several potent and selective compounds have been synthesized and studied in vitro and in vivo. In experimental animals with a stimulated renin-angiotensin system the haemodynamic effects of renin inhibitors have been shown to be identical to those of angiotensin-converting enzyme inhibitors. The two classes of agents also have similar antihypertensive effects in various forms of experimental renal hypertension. However, it is not clear whether then efficacy will be comparable in patients with essential hypertension. The main shortcoming of the currently available renin inhibitors is their low bioavailability after oral administration and their short duration of action. The improvement of these pharmacokinetic properties is the main challenge for future research in this area.

Altered calcium regulation in the cardiac plasma membrane in experimental renal hypertension

The factors regulating calcium homeostasis in the cardiac plasma membrane of renal hypertension in the rat (two kidney-one clip, Goldblatt model) have been studied. Comparison of the cardiac sarcolemma from control (C) and hypertensive (H) rats indicates similar protein yield and purity. Study of longer term hypertension (4 to 12 weeks) shows a decrease in the number of calcium channel receptor binding sites (Bmax C: 549 +/- 122 fmol/mg; H: 334 +/- 74 fmol/mg) as well as a depressed calcium pumping ATPase activity (C: 7.6 +/- 2.5 nmol/mg/min; H: 3.8 +/- 1.5 nmol/mg/min). Furthermore, there is a decreased rate of Na+-Ca2+ exchange (C: 5.4 +/- 1.9 nmol/mg/5 s; H: 2.3 +/- 0.9 nmol/mg/5 s). Study of short-term hypertension (1 to 4 weeks) indicates that the earliest change occurs at 1 week with decreased calcium pumping ATPase due to a change of the Vmax of Ca2+ transport (C: 9.7 +/- 1.6 nmol/mg/min; H: 5.4 +/- 1.4 nmol/mg/min). This is then followed by the decreased calcium channel receptor binding. However, the rate and the extent of depression in Ca2+-ATPase activity are much greater than that of Ca2+ channel receptor binding. Since alteration of Ca2+-ATPase is accompanied by an increase in intracellular Ca2+ concentration and there is a temporal association with the onset of myocardial lesions in the hypertensive rats, it is suggested that elevated intracellular calcium concentration as a result of altered Ca2+-ATPase activity may play a significant role in the development of hypertensive cardiomyopathy.

Connective tissue analysis of the canine circle of Willis in hypertension.

The collagen and elastin contents of the major arterial components of the canine circle of Willis (basilar artery, posterior cerebral artery, internal carotid artery, middle cerebral artery, and anterior cerebral artery) were determined as measures of the passive mechanical properties of these vessels. Studies were carried out in seven normotensive dogs and seven dogs in which experimental renal hypertension of 3 months duration had been induced. In the normotensive animals, the collagen content of the middle cerebral artery exceeded that of the other vessels considered. The elastin content and the total connective tissue were not significantly affected by arterial site. The middle cerebral artery collagen to elastin ratio was greater than corresponding values for the basilar, posterior cerebral, and internal carotid arteries. Connective tissue differences were less pronounced in the hypertensive animals. No component of the canine circle of Willis in the hypertensive dogs showed a significantly different collagen content, elastin content, total connective tissue content, or collagen to elastin ratio. In comparing cerebral vessels from normotensive and hypertensive dogs, total connective tissue values were greater in hypertension for all arterial sites considered. These acute physiological changes in connective tissue content over small distances in intracranial blood vessels from normotensive animals, together with unique connective tissue responses of these vessels to short term hypertension, may suggest additional possible factors important in the natural history of cerebrovascular pathological conditions.