Arterial Hypertension In Dogs Research Articles

Evaluation of albuminuria and its relationship with blood pressure in dogs with chronic kidney disease

Microalbuminuria and hypertension have long been associated with a guarded prognosis in human patients with a variety of diseases. In veterinary medicine, tests for microalbuminuria have been used for detecting early kidney damage, but there is little information regarding its association with high blood pressure in dogs with chronic kidney disease (CKD). The objective of this study was to evaluate albuminuria and its association with arterial hypertension in dogs with CKD. Urinary albumin:creatinine (UAC) ratio, urinary protein:creatinine (UPC) ratio, and systolic blood pressure were determined in 39 clinically healthy dogs and 40 dogs with CKD. UAC in dogs with CKD (range, 0.002-7.99; median, 0.38) was statistically different from that of control dogs (range, 0.0005-0.01; median, 0.002). Microalbuminuria (UAC 0.03-0.3) and macroalbuminuria (UAC>0.3) were detected in 32.5% and 50% of dogs with CKD, respectively. Sixty percent (24/40) of dogs with CKD had systolic pressure > or =180 mmHg; in these dogs, UAC ratio (range, 0.006-7.99; median, 1.72) was significantly higher than in dogs with CKD and systolic pressure<180 mmHg (range, 0.002-4.83; median, 0.10). Of hypertensive dogs with CKD, those with UPC>1.0 usually had macroalbuminuria, those with UPC 0.5-1.0 usually had microalbuminuria, and those with UPC<0.5 usually lacked albuminuria. UAC ratio was higher in hypertensive than in normotensive dogs with CKD. Tests designed to detect microalbuminuria may be useful for hypertensive dogs with CKD and a UPC < or = 1.0 to detect the onset and magnitude of albuminuria. Once macroalbuminuria is overt, the UPC ratio itself can be used for the same purpose.

Clinical Efficacy of Sildenafil in Treatment of Pulmonary Arterial Hypertension in Dogs

Pulmonary arterial hypertension (PAH) in dogs carries a poor prognosis. Sildenafil increases exercise capacity and improves hemodynamics in people with PAH. Dogs receiving sildenafil will have lower pulmonary arterial pressure, increased exercise capacity, and better quality of life (QOL) than dogs receiving placebo. Thirteen dogs with echocardiographic evidence of PAH. Prospective short-term, randomized, placebo controlled, double-blind, crossover study. Dogs with PAH were randomly allocated to receive sildenafil or placebo for 4 weeks, followed by the alternative treatment for 4 weeks. Dogs receiving sildenafil had a significantly lower estimated pulmonary arterial pressure (median, 56 mmHg; range, 34-83 mmHg) than at baseline (median, 72 mmHg; range, 61-86 mmHg; P=.018), but not significantly lower than those receiving placebo (median, 62 mmHg; range, 49-197 mmHg). Exercise capacity was significantly greater in dogs receiving sildenafil than those receiving placebo (mean activity count per minute: 101+/-47 versus 74+/-32; P=.05). QOL scores were significantly higher in dogs receiving sildenafil than dogs receiving placebo. Sildenafil decreases systolic pulmonary arterial pressure from baseline in dogs with PAH and is associated with increased exercise capacity and QOL when compared to treatment with placebo.

Pulmonary arterial hypertension secondary to chronic left‐sided cardiac dysfunction in dogs

Pulmonary arterial hypertension is a description of a physiological finding rather than a diagnosis. Pulmonary arterial pressure is the result of interactions among pulmonary blood flow (right ventricular cardiac output), pulmonary vascular impedance and post-capillary pressure (typically reflecting left atrial pressure). When elevations in pulmonary arterial pressure (systolic/diastolic pulmonary arterial pressure > approximately 30/19 mmHg at rest) are accompanied by increased left atrial pressure, pulmonary arterial hypertension may be considered secondary to left-heart failure. Introduction of Doppler methods to diagnose pulmonary arterial hypertension has increased the awareness of the prevalence and importance of pulmonary arterial hypertension dogs with left-heart failure. Increasing understanding of the mechanism of development of pulmonary venous hypertension and reactive pulmonary arterial hypertension in dogs with left-heart disease has led to the development of successful additive therapies for progressive clinical signs in the setting of chronic therapy for congestive heart failure due to left-sided valvular and myocardial dysfunction. Because effective therapies for pulmonary arterial hypertension secondary to chronic left-sided cardiac dysfunction are now available, screening for pulmonary arterial hypertension should be a regular part of the Doppler echocardiographic examination in a clinical setting of chronic therapy for left-sided congestive heart failure due to valvular or myocardial disease.

Avaliação da albuminúria e da eletroforese de proteínas urinárias de cães com hiperadrenocorticismo e a relação com a pressão arterial sistêmica

O hiperadrenocorticismo é uma das endocrinopatias mais comuns em cães, sendo caracterizado pela exposição excessiva de glicocorticóides secretados pelas adrenais. A hipercortisolemia crônica pode promover várias complicações, incluindo hipertensão sistêmica e glomerulonefrite. A glomerulonefrite pode desencadear variáveis graus de proteinúria e uma tendência de evolução para doença renal crônica. A perda de proteínas na urina, principalmente da albumina, é uma característica das doenças glomerulares e a determinação de variáveis laboratoriais, como a razão proteína:creatinina urinária (RPC), albuminúria (teste de ELISA) e eletroforese das proteínas urinárias, são recomendadas para a elucidação do diagnóstico. Assim, o objetivo do estudo é avaliar a relação entre proteinúria e hipertensão arterial sistêmica em cães com hiperadrenocorticismo e verificar, pela avaliação da albuminúria e do peso molecular das proteínas urinárias, o segmento do néfron que foi comprometido ou lesado. Foram avaliados 30 cães com diagnóstico de hiperadrenocorticismo, subdivididos em 13 cães com hipertensão arterial sistêmica (grupo I) e 17 cães normotensos (grupo II). Foram determinados a RPC; a albuminúria pela avaliação da albumina normalizada e razão albumina:creatinina urinária (RAC) e a eletroforese de proteínas pela técnica em gel de poliacrilamida, contendo dodecil sulfato de sódio (SDS-PAGE). Os resultados foram comparados com os dados obtidos de 30 cães clinicamente saudáveis. Foi constatado que não houve influência da hipertensão arterial sistêmica nos cães com hiperadrenocorticismo em relação à quantificação da albuminúria, determinada pelo método ELISA, e nem na qualidade e quantidade das bandas de proteínas de baixo (&lt;60 kDa) e de alto peso molecular (&gt;60 kDa). No entanto foi determinado que cães com hiperadrenocorticismo podem desenvolver lesões glomerulares e tubulares, caracterizadas pela presença de albuminúria e de proteínas de alto e de baixo pesos moleculares, independentemente da presença de hipertensão arterial sistêmica. Conclui-se que a avaliação quantitativa (RPC e RAC) e qualitativa (SDS-PAGE) das proteínas urinárias traz informações adicionais que indicam os possíveis segmentos comprometidos dos néfrons que causaram as perdas de proteínas na urina.

Doppler echocardiography–derived evidence of pulmonary arterial hypertension in dogs with degenerative mitral valve disease: 86 cases (2001–2005)

To determine the prevalence of Doppler echocardiography-derived evidence of pulmonary arterial hypertension (DEE-PAH) in dogs with mitral valve disease (MVD) classified according to the International Small Animal Cardiac Health Council (ISACHC) heart failure classification scheme and various echocardiographic and Doppler indices of MVD severity. Retrospective case series. 617 dogs examined from 2001 to 2005 with MVD in ISACHC classes I to III. Dogs were examined echocardiographically. Criteria used for systolic and diastolic DEE-PAH were detection of high tricuspid (> or = 2.5 m/s) and telediastolic pulmonic (> or = 2.0 m/s) valvular peak regurgitant jet velocities, respectively, by use of continuous-wave Doppler echocardiography. 86 (13.9%) dogs with MVD had a diagnosis of DEE-PAH. Severity and prevalence of DEE-PAH increased with ISACHC class (3.0%, 16.9%, 26.7%, and 72.2% prevalences for ISACHC classes Ia, Ib, II, and III, respectively). A significant correlation between systolic or diastolic pulmonary arterial pressure and left atrial-to-aortic diameter ratio (LA/Ao) was detected. Doppler echocardiography-derived evidence of pulmonary arterial hypertension was detected in 18 dogs with values of LA/Ao within reference range, all of which had moderate (n = 2 dogs) or severe (16) mitral valve regurgitation on color Doppler imaging. The prevalence and degree of DEE-PAH were related to the severity of MVD. Changes associated with DEEPAH may be detected in early stages of the disease, but only in dogs with severe mitral valve regurgitation.

ACUTE CARDIOPULMONARY EFFECTS OF A DUAL–ENDOTHELIN RECEPTOR ANTAGONIST ON OLEIC ACID–INDUCED PULMONARY ARTERIAL HYPERTENSION IN DOGS

The objective of this study was to evaluate the cardiopulmonary effects of a dual–endothelin (ET) receptor antagonist, Tezosentan, on oleic acid (OA)-induced acute lung injury with pulmonary arterial hypertension in dogs. Twelve pentobarbital-anesthetized dogs with intravenous OA-induced acute lung injury (ALI) were divided into 2 groups. The control group (n = 6) received saline treatment, whereas the treatment group (n = 6) received the ET receptor antagonist, Tezosentan (1 mg/kg intravenous [IV] + 1 mg/kg/h IV infusion). Cardiopulmonary parameters were monitored continuously for 1 hour. OA administration resulted in a significant increase in mean pulmonary arterial pressure (MPAP) and pulmonary vascular resistance (PVR) and a decrease in mean systemic arterial pressure (MSAP), systemic vascular resistance (SVR), and cardiac output (CO) in all dogs. Tezosentan treatment markedly attenuated the pulmonary hypertension, with a 32% decrease in MPAP (from 23±2 mm Hg to 15±2 mm Hg; P < .01) and a 22% decrease in PVR (from 860±105 dyn · s · cm−5to 670±96 dyn · s · cm−5; P < .01) at the end of study. MSAP and SVR were unchanged after Tezosentan treatment, and there was an increase in cardiac output and a decline in peak inspiratory pressure (PIP) in the Tezosentan group compared with the control group. These results indicate that the dual–ET receptor antagonist, Tezosentan, can attenuate the pulmonary hypertension induced by OA. Thus, dual–ET receptor antagonists such as Tezosentan may be useful in the management of acute pulmonary arterial hypertension, complicating the course of OA-induced lung injury.

Effect of transitory brain ischemia on the synthesis of prostacyclin in arterial hypertension in dogs

Acute and chronic brain ischemia in dogs with rehabilitated hypertension is modeled by applying a tourniquet on the carotid artery. Occlusion of the coronary artery (60 and 120 min for 12 days) induces ischemic stress. Brain ischemia is accompanied by a decrease in plasma prostacyclin and the development of platelet hyperaggregation, which can produce thrombogenesis. The calcium antagonist nifedipine produces stress- and prostacyclin-protective effects by reducing platelet hyperaggregation and preventing thrombogenesis.

Cerebral blood flow and cerebral blood flow velocity during angiotensin-induced arterial hypertension in dogs.

Pressure-passive perfusion beyond the upper limit of cerebral blood flow (CBF) autoregulation may be deleterious in patients with intracranial pathology. Therefore, monitoring of changes in CBF would be of clinical relevance in situations where clinical evaluation of adequate cerebral perfusion is impossible. Noninvasive monitoring of cerebral blood flow velocity using transcranial Doppler sonography (TCD) may reflect relative changes in CBF. This study correlates the effects of angiotensin-induced arterial hypertension on CBF and cerebral blood flow velocity in dogs. Heart rate (HR) was recorded using standard ECG. Catheters were placed in both femoral arteries and veins for measurements of mean arterial blood pressure (MAP), blood sampling and drug administration. A left ventricular catheter was placed for injection of microspheres. Cerebral blood flow velocity was measured in the basilar artery through a cranial window using a pulsed 8 MHz transcranial Doppler ultrasound system. CBF was measured using colour-labelled microspheres. Intracranial pressure (ICP) was measured using an epidural probe. Arterial blood gases, arterial pH and body temperature were maintained constant over time. Two baseline measures of HR, MAP, CBF, cerebral blood flow velocity and ICP were made in all dogs (n = 10) using etomidate infusion (1.5 mg.kg-1 x hr-1) and 70% N2O in O2 as background anaesthesia. Following baseline measurements, a bolus of 1.25 mg angiotensin was injected i.v. and all variables were recorded five minutes after the injection. Mean arterial blood pressure was increased by 76%. Heart rate and ICP did not change. Changes in MAP were associated with increases in cortical CBF (78%), brainstem CBF (87%) and cerebellum CBF (64%).(ABSTRACT TRUNCATED AT 250 WORDS)

Is neuropeptide Y co-released with catecholamines in experimental arterial hypertension following sinoaortic denervation?

The release of catecholamines and their coneurotransmitter neuropeptide Y (NPY) was investigated in conscious dogs with neurogenic arterial hypertension elicited by sinoaortic denervation. One month after denervation, an elevation of catecholamine levels (measured by HPLC) without elevation of NPY-like immunoreactivity (NPY-LI) levels in plasma (evaluated by RIA) has been found. This dissociation could be explained by 1) a transient release of NPY during the first weeks after surgery, 2) a depletion of neuronal NPY due to the permanent sympathetic stimulation, or 3) an insufficient increase in sympathetic tone. To test these hypotheses, we investigated the time courses of catecholamine and NPY-LI levels in arterial plasma during the first five weeks after sinoaortic denervation and responses to yohimbine (an alpha 2 antagonist which enhances transmitter release). Resting NPY-LI levels in plasma remained normal during the first five weeks after sinoaortic denervation. In normal dogs, a high dose of yohimbine (0.5 mg/kg i.v.) elevated both catecholamine (6-fold) and NPY-LI levels (1.5-fold), whereas a lower dose (0.05 mg/kg i.v.) induced a two fold elevation of catecholamine levels without changing NPY-LI concentrations. In sinoaortically denervated dogs, yohimbine elicited elevation of both catecholamines and NPY-LI whatever the dose used. Thus, neurogenic arterial hypertension in dogs seems to involve catecholamines but not NPY. Moreover, the present work suggests that a high level of sympathetic stimulation is required for a co-release of catecholamines and NPY.

Arterial hypertension in dogs with experimental informational pathology of their higher nervous activity.

It is shown that stable arterial hypertension can be formed in dogs by the development of experimental pathology of higher nervous activity (behavior) as a result of prolonged brain work during exposure to a combination of three unfavorable factors: a large volume of information to be processed and assimilated, shortage of time allowed for the work, and a high level of motivation of behavior. Three types of development of arterial hypertension were found, correlating with changes in behavior; self-regulating behavior reflecting defensive activity of the brain is particularly interesting. A high degree of self-regulating behavior was found to increase the resistance of the animal to arterial hypertension but weakening of self-regulation of behavior facilitates its onset and development.

Role of the renin-angiotensin system in renal hypertension. An experimental approach.

In 1898 Tigerstedt and Bergman first detected the existence of renal renin and discussed its possible role in the development of cardiac hypertrophy associated with various kidney diseases. Hartwich (1930) and Goldblatt et al. (1934) were able to produce persistent arterial hypertension in dogs by narrowing the renal arteries. Subsequently, a large number of findings accumulated in the field of renal hypertension. Most of the material has been covered in reviews edited by Braun-Menendez (1946), Page and McCubbin (1968), and Page and Bumpus (1974). There is general agreement that arterial hypertension, including renal hypertension, is a multifactorial disorder of regulation as anticipated by Page in 1949 when he proposed his concept known as the mosaic theory.

Dimensional changes of the left ventricle during acute pulmonary arterial hypertension in dogs

Left ventricular dimensions and volumes were measured by an endocardial marker technique in eight closed chest dogs during progressive increases of 10 mm Hg in mean pulmonary arterial pressure. Right ventricular volumes were measured by biplane cineanglography. Increasing mean pulmonary arterial pressure caused a progressive increase in right ventricular volume; at a mean pulmonary arterial pressure of 60 mm Hg, right ventricular end-diastolic volume increased by 48 percent and end-systolic volume by 50 percent. Left ventricular volumes began to decrease significantly at a mean pulmonary arterial pressure of 30 mm Hg, and when a mean pulmonary arterial pressure of 60 mm Hg was reached, left ventricular end-diastolic volume had decreased by 30 percent and left ventricular end-systolic volume by 19 percent. Changes in ventricular filling pressure dlrectionally followed the volume changes of the respective ventricle. Left ventricular stroke volume decreased 45 percent at a mean pulmonary arterial pressure of 60 mm Hg but increasing heart rate prevented a decrease in cardiac output. The decrease in left ventricular volume as pulmonary arterial pressure was Increased was associated with a disproportionate reduction in the left ventricular septal-lateral axis. At end-diastole, this dimension decreased by 22 percent at a mean pulmonary arterial pressure of 60 mm Hg, the anterior-posterior axis decreased by 8 percent and the base-apex axis by 4 percent. A similar disproportionate decrease of the septal-lateral axis occurred at end-systole. Even at the modest increase in mean pulmonary arterial pressure to 20 mm Hg, only the septal-lateral dimension was significantly shortened, and the right ventricular end-diastolic volume had increased by 17 percent but left ventricular end-diastolic volume was not significantly changed. Thus, during acute pulmonary hypertension, the right ventricle progressively dilates resulting in a distinctive change in the shape of the left ventricle that suggests septal buiging and that may impair left ventricular function.

Arterial hypertension in dogs. I. Methods.

Various methods were devised in attempts to produce chronic hypertension in dogs. The induction of anxiety was unsuccessful. Bilateral renal denervation combined with injections of epinephrine appeared to produce temporary hypertension. Permanent hypertension was induced by unilateral renal ischemia with the other kidney left intact only in dogs of nervous temperament. Certain dogs were extremely resistant to the development of hypertension even when several methods were combined. Neurogenic hypertension induced by section of the moderator nerves is probably a true hypertension. It is obvious that the host factor may be as important as the method employed.

Production of prolonged arterial hypertension in dogs by chronic stimulation of the nervous system; exploration of the mechanism of hypertension accompanying increased intracranial pressure.

We were unable to produce chronic arterial hypertension in dogs by severe cerebral ischemia induced by ligation of blood supply to the brain. Combining cerebral ischemia with the mechanical effect of a wire in the floor of the fourth ventricle and the thermal stimulus of heat generated in this wire by short wave diathermy resulted in hypertension that lasted as long as 10 months. Experiments are described which indicate that the arterial hypertension which accompanies increased cerebrospinal fluid pressure is in part the result of pressure on the brain and not entirely due to cerebral anemia.