Normotensive Control Dogs Research Articles

Possible association of glaucoma with pectinate ligament dysplasia and narrowing of the iridocorneal angle in Shiba Inu dogs in Japan

The purpose of the study was to describe the shape of the pectinate ligament (PL) and to estimate the width of the iridocorneal angle (ICA) in glaucomatous and non-glaucomatous eye of Shiba Inu dogs in Japan. One hundred fourteen Shiba Inu dogs were presented to the Veterinary Medical Center at the University of Tokyo between June 1998 and June 2003. Among these, 46 dogs had glaucoma; the remaining 68 dogs were presented for routine vaccinations or heartworm testing and were used as a control population. Complete ophthalmic examination and gonioscopy were performed in all the dogs. PL and ICA were evaluated by gonioscopy and goniophotographs. Of the 46 dogs with glaucoma, 17 (37%) were affected bilaterally, and 29 (63%) were affected unilaterally. Of the 29 dogs with unilateral glaucoma, the ICA of the normotensive eye was slightly narrow in 2 eyes (7%), narrow in 12 eyes (41%), and closed in 15 eyes (52%). Among the normotensive control group, the ICA was open in 13 dogs (19%), slightly narrow in 29 (43%), narrow in 22 (32%), and closed in 4 (6%). In dogs with narrow and slightly narrow ICAs, the PLs were thickened, and in some cases, formed a solid sheet. The majority of dogs with glaucoma had changes in both ICA and PL. A narrow or slightly narrow ICA was also detected in the majority of normotensive control dogs. This study suggests that ICA narrowing and PL thickening is a common abnormality in Shiba Inu dogs in Japan and may predispose those dogs to glaucoma.

Platelet aggregation and dense granule secretion in a colony of dogs with spontaneous hypertension.

Since canine hereditary essential hypertension has been previously reported in a colony of Siberian husky dogs, we tested the suitability of this model for use in studies on the platelet defect identified in humans with essential hypertension. Platelet aggregation and dense granule ATP secretion were measured in dogs with essential hypertension and normotensive control dogs. The platelets from the hypertensive group showed significantly increased aggregation and secretion in response to stimulation with ADP. There was no significant increase in aggregation or secretion when platelets from hypertensive dogs were stimulated by platelet-activating factor, thrombin, calcium ionophore A23187 or phorbol myristate acetate. The increased aggregation and secretion responses in platelets from the hypertensive dogs suggest that a defect similar to that reported in humans with essential hypertension exists and that further investigation is warranted.

Epidemiology and prevention of blood pressure-related renal disease

To examine the relationship between blood pressure and end-stage renal disease. Review of recent reports on blood pressure in relation to renal function. The incidence and prevalence of treated end-stage renal disease are increasing progressively in economically developed countries. To combat this problem, the treatment of established end-stage renal disease must be complemented by strategies to treat and prevent risk factors for the development of renal failure. Severe hypertension and malignant hypertension are well accepted as risk factors for renal insufficiency. Recent reports suggest a strong relationship between blood pressure and renal function, throughout the entire range of blood pressure. Most blood pressure-related renal disease can probably be attributed to mild hypertension or a high normal blood pressure. Additional clinical trials are needed to assess the value of different antihypertensive drugs and different levels of blood pressure control in preserving renal function in subjects at risk of blood pressure-related renal disease. Primary prevention of hypertension may be an important complement to the treatment of established hypertension in reducing the burden of renal disease in the community.

Hypertensive dog plasma inhibits the Na+-K+ pump of cultured vascular smooth muscle.

We investigated the effects of plasma from dogs with perinephritic hypertension on the Na+-K+ pump of cultured dog vascular smooth muscle cells. We also measured [3H]ouabain binding by myocardium and vascular tissue. Fresh, unprocessed plasma from healthy dogs during the first 6 weeks of benign one-kidney, one wrapped hypertension and from paired normotensive control dogs was layered over confluent primary cultured puppy aortic smooth muscle cells that had been sodium-loaded with monensin. In 26 paired assays of plasma from four pairs of dogs, cells incubated in the presence of plasma from hypertensive dogs had significantly reduced total (p less than 0.01) and ouabain-sensitive (p less than 0.001) 86Rb+ uptakes, but their intracellular sodium content did not differ from cells incubated in paired normotensive plasma. We no longer detected these uptake differences when passaged cells or cells cocultured with bovine endothelial cells were used for assay or when plasma was treated with protease inhibitors or boiled. However, boiled plasma increased the sodium content of the assay cells, suggesting an ionophorelike effect. Levels of pump inhibitory activity in plasma appeared to remain constant during Weeks 1 to 6 of hypertension. We found no evidence for altered numbers of pump sites in cardiovascular tissues from these hypertensive dogs. These findings support the hypothesis that plasma factors inhibit the membrane Na+-K+ pump in vascular smooth muscle cells in this form of hypertension. These plasma inhibitory factors apparently do not induce pump molecules.

Decreased intraocular pressure in dogs with one-kidney, one wrapped hypertension.

We examined the relationship of intraocular pressure and the development of one-kidney, one wrapped (perinephritic) hypertension in the dog. Conscious femoral arterial pressure (direct arterial puncture) and intraocular pressure (Schiotz tonometer) were measured weekly before and after the surgical induction of hypertension in 11 healthy male mongrel dogs and before and after unilateral nephrectomy in 15 normotensive control dogs. Preoperative mean arterial pressure (102 +/- 5 vs 99 +/- 8 [SD] mm Hg, hypertensive vs control dogs) and intraocular pressure (18.1 +/- 2.5 vs 17.7 +/- 2.1 mm Hg, hypertensive vs control dogs) were similar in both groups. In normotensive control dogs, mean arterial pressure and intraocular pressure averaged over the postoperative period (4-8 weeks) did not differ significantly from preoperative values. In contrast, during the same period arterial pressure significantly increased and intraocular pressure significantly decreased in hypertensive dogs (arterial pressure, 163 +/- 8 mm Hg; intraocular pressure, 11.9 +/- 4.0 mm Hg; p less than 0.001 for both values compared with corresponding values in control dogs). Intraocular pressure was inversely related to arterial pressure in hypertensive dogs (r = 0.56, p less than 0.01). These observations indicate that intraocular pressure decreases with the development of canine one-kidney, one wrapped hypertension. The mechanism of this decrease may be related to abnormalities in Na+,K+-adenosine triphosphatase activity found in this form of hypertension.

Cardiopulmonary hemodynamics in perinephritic hypertensive dogs: effect of intravenous volume load.

To investigate the role of decreased venous distensibility in the regulation of cardiac output, cardiopulmonary hemodynamic measurements were performed at rest and after a volume load (6% dextran in saline, 12 ml/kg iv) in 18 awake dogs with chronic one-kidney, one-wrapped hypertension and 9 normotensive control dogs. The distribution of blood volume between the peripheral and cardiopulmonary vascular beds and the increase in cardiac output after volume load in the two groups of dogs were the same. There was no echocardiographic evidence of left ventricular dysfunction (shortening fraction) in hypertensive dogs. The rise of heart rate after volume load in hypertensive dogs, 17 +/- 3 beats/min (mean +/- SE), was attenuated compared to that of control dogs, 38 +/- 4 (p less than 0.001). Compared to values in normotensive dogs, the in vitro left atrial pressure-volume curves of hypertensive dogs were shifted in the direction of the pressure axis (p less than 0.02). The findings do not provide a role for decreased venous distensibility in the regulation of cardiac output in chronic renal hypertension. Decreased distensibility of the left atrium may play a role in the pathogenesis of the attenuated Bainbridge effect in hypertensive dogs.

Echocardiographic evidence for increased cardiac performance during early renal hypertension in dogs.

Cardiac function early (less than 4 weeks) in the course of experimental renal hypertension was investigated. In 11 male mongrel dogs, one kidney was wrapped in silk to produce two-kidney, one-wrapped hypertension. Two weeks later, the contralateral kidney was removed. Five sham-wrapped and then contralaterally-nephrectomized dogs served as controls. M-mode left ventricular (LV) echocardiograms were recorded twice weekly in all dogs for 4 weeks before and for 2 weeks after wrapping (or sham-wrapping) and for 4 weeks after nephrectomy. In the 11 hypertensive dogs, mean arterial pressure (MAP) rose from 127 mm Hg (mean) to 143 two weeks after wrapping (p less than 0.05) and to 185 two weeks after nephrectomy (p less than 0.001). The fractional shortening of the left ventricle (% delta D) of hypertensive dogs was increased (9% maximum, mean, p less than 0.01) for 2 weeks after wrapping and for one week after nephrectomy. Two weeks after wrapping, LV end-systolic wall stress calculated from femoral artery peak systolic pressure, end-systolic dimension and wall thickness was unchanged, suggesting that increased myocardial contractility accounted for the findings. In normotensive control dogs, there were no echocardiographic changes during the study.

Echocardiographic assessment of left ventricular hypertrophy and function in renal hypertensive dogs.

To investigate the performance of the hypertrophied left ventricle, M-mode echocardiographic measurements were performed 2 to 3 times weekly on 8 unanesthetized dogs for several weeks before and for 6 months after the induction of perinephritic hypertension. Four dogs with sham-wrapping and contralateral nephrectomy served as the controls. From a baseline value of 7.7 +/- 0.4 mm (mean +/- SD), left ventricular wall thickness increased to 9.0 +/- 0.6 mm (p less than 0.001) by the 4th week after the induction of hypertension and reached a plateau of 10.2 +/- 1.2 mm (p less than 0.001) by week 10. Fractional shortening of left ventricular dimension (% delta D) increased during early left ventricular hypertrophy and remained elevated for 6 months in the surviving 6 hypertensive dogs. In hypertensive dogs, left ventricular concentric hypertrophy became detectable by week 6 of hypertension. Control dogs did not show these changes. At autopsy, the left ventricular weight of hypertensive and normotensive control dogs was (6.2 +/- 1.4 g/kg and 4.3 +/- 0.5 g/kg (p less than 0.05). In summary, during the early stage of left ventricular hypertrophy in renal hypertensive dogs cardiac performance increased. There is no evidence for deterioration of left ventricular performance as concentric left ventricular hypertrophy develops and becomes chronic.

Angiopathic serum factor in perinephritic hypertensive dogs.

To investigate the role of circulating humoral substances in the pathogenesis of increased vascular wall water and sodium concentration in experimental hypertension, rabbit aortic media explants were cultured in tissue culture medium supplemented (10-20%) with serum obtained from the same dogs (n = 7): 1) before the induction of hypertension; 2) after wrapping one kidney in silk (two-kidney perinephritic hypertension, 2-KPHT); and 3) after contralateral nephrectomy (1-KPHT). Cultures also were run with serum of sham-wrapped and then unilaterally nephrectomized normotensive dogs (n = 4). After 3 weeks of culture, the explants were harvested, and their water, sodium and potassium concentration was measured. Compared to the composition of explants cultured in prehypertensive serum, the water concentration of explants cultured in 1-KPHT and the sodium concentration of explants cultured in 2-KPHT and 1-KPHT serum were increased (p < 0.05). The water and electrolyte content of explants cultured in sera of sham-operated normotensive control dogs was the same regardless of the type of serum used, pre- or post-sham surgery or post-nephrectomy. The effects of serum from hypertensive dogs were not explained by variations in serum creatinine, sodium and potassium levels or in plasma renin activities. The experiments provide evidence for the role of serum factor(s) in the pathogenesis of abnormal vascular wall water and sodium concentration in experimental hypertension.

Depressed function of a ouabain-sensitive sodium-potassium pump in blood vessels from renal hypertensive dogs.

Vasodilator responses to acute intra-arterial infusions of K+ are attenuated in dogs with chronic one-kidney perinephritic hypertension in rats with chronic two-kidney Goldblatt hypertension, and in men with essential hypertension. There is evidence that K+ evokes vasodilation by stimulating vascular smooth muscle membrane Na+-K+-activated adenosine triphosphatase, thereby increasing activity of the cellular Na+-K+ electrogenic pump. We therefore proposed that there may be an underlying decrease in the operation of this pump in vascular smooth muscle of hypertensives. The operation of the cellular Na+-K+ pump may be estimated by measurement of rubidium uptake. Thus, so further investigate our hypothesis, we measured 86Rb uptake in small mesenteric arteries and splanchnic veins from 12 dogs with chronic uncomplicated one-kidney perinephritic hypertension and from 12 normotensive control dogs. Vessels were excised under thiamylal anesthesia and incubated in cold medium (plasma or Krebs-Henseleit solution) for sodium loading and then the velocity of 86Rb uptake was estimated in the absence of or in the presence of ouabain, a specific inhibitor of the Na+-K+ pump. In neither arteries nor veins was there evidence for differences between hypertensives and normotensives in the ouabain-insensitive uptake of 86Rb. In contrast, the ouabain-sensitive 86Rb uptake was depressed by 42% in arteries (P less than 0.05) and by 49% in veins (P less than 0.01) from hypertensive dogs, if incubated in the dog's own plasma. These results indicate that the activity of a ouabain-sensitive Na+-K+ pump may be depressed in vascular tissue from dogs with chronic one-kidney perinephritic hypertension. Because the Na+-K+ pump in vascular smooth muscle is probably electrogenic, such an abnormality, by partially depolarizing the muscle cell membrane, would help to account for the elevated vascular resistance found in these dogs.

Decreased venous compliance in dogs with chronic renal hypertension.

Femoral vein (FV) pressure-volume relationships were measured in vitro in 14 dogs with chronic (more than 4 weeks), one-kidney perinephritic hypertension and in 13 unilaterally nephrectomized normotensive control dogs. Segments of FV were also examined histologically and analyzed for their water and electrolyte contents. Compared to controls: (I) the FV pressure-volume curves of hypertensive dogs were shifted toward the pressure axis (P is less than 0.05); (ii) calcaulated vagous compliance in the pressure range of 0-15 mm Hg was decreased (P is less than 0.05); and (iii) the water and sodium contents of vwins from hypertensive dogs were increased (P is less than 0.05). Histological examination of the FV from hypertensive and control dogs did not reveal significant differences. The findings indicate that the decreases in venous compliance that we have previously observed in the early stages (less than 4 weeks) of perinephritic hypertension in dogs persist into the chronic stage of hypertension. Venous wall "edema" may account for the decreased venous compliance in this form of hypertension.

Experimental renal hypertension in dogs. Forelimb hemodynamics.

Blood flow arid segmental intravascular pressures were measured in the pump-perfused forelimb vascular beds of 25 dogs with chronic perinephritic hypertension and 26 normotensive control dogs (either unilaterally nephrectomized or sham-operated) under pentobarbital anesthesia. Measurements were made under resting conditions (pump-perfusion pressure set equal to aortic pressure) and during response to: (1) stepwise changes in pump blood flow over the range 21-330 ml/min; (2) intrabrachial arterial injection of supramaximal doses of methacholine chloride; and (3) limb denervation. Total limb vascular resistance and segmental pressure gradients were calculated. In hypertensive dogs, as compared to normotensive dogs, resting blood flow was equal ( P &gt;0.3) and resting limb total vascular resistance was increased ( P &lt;0.005). Small vessel pressure gradient was increased ( P &lt;.005) and venous pressure gradient was decreased ( P &lt;0.005). Limb vascular resistance following methacholine injections and residual resistance following neurectomy were lower ( P &lt;0.05) in normotensive than in hypertensive dogs. The development of hypertension was accompanied by the upward displacement of limb flow-resistance curves without discernible change in shape of the curves. These data suggest that in chronic renal hypertension in dogs: (1) the limb vascular bed participates in the increased peripheral vascular resistance; (2) the increase in limb vascular resistance is confined to the small vessel segment with no evidence found for limb venoconstriction; (3) a portion of the elevated limb vascular resistance is not attributable to neural stimuli; and (4) structural changes in vessels may account for part of the increase in limb resistance.

NA AND K BOUND TO AN ETHER SOLUBLE COMPOUND IN MYOCARDIUM OF RENAL HYPERTENSIVE DOGS.

The sodium and potassium contained in a phospholipid extract of tissue were determined on tissues of renal hypertensive and operated normotensive control dogs. Hypertension produced an increase in the sodium contained in a phospholipid extract of left ventricle. There was a slight but not statistically significant increase in the sodium bound in the phospholipid extract of the right ventricle. There was potassium bound by these phospholipids but the amount did not change significantly in either ventricle in hypertension.

Antihypertensive Effect of Hypophysectomy in Dogs with Hypertension Following Bilateral Carotid Sinus Constriction

A chronic type of experimental hypertension has been produced in dogs by bilateral sinus area constriction. Hypophysectomy has a prolonged antihypertensive effect in dogs with persistent hypertension resulting from carotid sinus area constriction, while no decrease in mean arterial pressure is seen after hypophysectomy in normotensive control dogs. These findings suggest the possibility that altered hypophyseal function participates in the pathogenesis of this type of hypertension.