Hypertensive Dogs Research Articles

Acute and chronic electrical activation of baroreceptor afferents in awake and anesthetized subjects

Electrical stimulation of baroreceptor afferents was used in the 1960's in several species, including human beings, for the treatment of refractory hypertension. This approach bypasses the site of baroreceptor mechanosensory transduction. Chronic electrical stimulation of arterial baroreceptors, particularly of the carotid sinus nerve (Hering's nerve), was proposed as an ultimate effort to treat refractory hypertension and angina pectoris due to the limited nature of pharmacological therapy available at that time. Nevertheless, this approach was abandoned in the early 1970's due to technical limitations of implantable devices and to the development of better-tolerated antihypertensive medications. More recently, our laboratory developed the technique of electrical stimulation of the aortic depressor nerve in conscious rats, enabling access to hemodynamic responses without the undesirable effect of anesthesia. In addition, electrical stimulation of the aortic depressor nerve allows assessment of the hemodynamic responses and the sympathovagal balance of the heart in hypertensive rats, which exhibit a well-known decrease in baroreflex sensitivity, usually attributed to baroreceptor ending dysfunction. Recently, there has been renewed interest in using electrical stimulation of the carotid sinus, but not the carotid sinus nerve, to lower blood pressure in conscious hypertensive dogs as well as in hypertensive patients. Notably, previous undesirable technical outcomes associated with electrical stimulation of the carotid sinus nerve observed in the 1960's and 1970's have been overcome. Furthermore, promising data have been recently reported from clinical trials that evaluated the efficacy of carotid sinus stimulation in hypertensive patients with drug resistant hypertension.

Pet Food Safety: Sodium in Pet Foods

Healthy dogs and cats appear to be able to adjust to differing amounts of sodium in their diet via the rennin-angiotensin-aldosterone mechanisms. There is no strong evidence that increased dietary sodium increases the risk of hypertension in dogs and cats, and the current recommendation for hypertensive animals is to avoid high dietary salt intake without making a specific effort to restrict it. The prevalence of salt sensitivity and its effect on blood pressure has not been determined for cats or dogs. The ideal amount of sodium in the diet of dogs and cats with cardiac deficiency has not been determined, as increasing may detrimentally increase the extracellular fluid volume, but decreasing it may detrimentally increase the activation of the rennin-angiotensin-aldosterone system. Increased dietary sodium increases urine output and may decrease the risk of forming calcium oxalate uroliths due to the decrease in relative supersaturation of solutes. However, caution should be used in increasing the sodium intake of patients with renal disease as increased dietary sodium may have a negative effect on the kidneys independent of any effect on blood pressure.

Ascites due to pre‐sinusoidal portal hypertension in dogs: a retrospective analysis of 17 cases

Accumulation of a pure transudate abdominal effusion in the absence of significant hypoalbuminaemia is uncommon in dogs and is due to pre-sinusoidal portal hypertension. Reported causes of pre-sinusoidal portal hypertension vary, but suggest a reasonable prognosis. A retrospective analysis of 17 dogs that presented to our institution with ascites due to pre-sinusoidal portal hypertension identified idiopathic hepatic fibrosis or canine chronic hepatitis as the underlying cause in the majority of cases. Twelve (70.5%) dogs were 4 years of age or younger at time of presentation. Total serum protein was higher in dogs with chronic hepatitis than it was in dogs without inflammatory disease. The prognosis was generally poor and no histological, imaging or biochemical parameters were useful as prognostic indicators. Dogs died or were euthanased due to severe clinical signs associated with the portal hypertension and/or perceived poor prognosis.

Development of Hypertension and Effects of Benazepril Hydrochloride in a Canine Remnant Kidney Model of Chronic Renal Failure

In order to determine whether hypertension would develop in dogs with chronic renal failure, we performed 7/8 renal ablation in 6 healthy dogs and compared pre- and post-ablation blood pressures determined by telemetry. One month after the renal ablation, blood urea nitrogen and creatinine were significantly increased (p<0.05), creatinine clearance was decreased (p<0.05), and blood pressure was increased significantly (p<0.05). Simultaneously, plasma renin activity, angiotensin I and II, and aldosterone were elevated significantly (p<0.05) compared with the values obtained from 11 healthy dogs with intact renal function. The dogs with induced renal failure and hypertension were administered an angiotensin-converting enzyme inhibitor, benazepril hydrochloride, once daily for 2 weeks at 2 mg/kg body weight, and changes in blood pressure and the renin-angiotensin-aldosterone (RAA) system were determined. During the administration of benazepril hydrochloride, blood pressure, angiotensin II and aldosterone decreased significantly (p<0.05) and, upon discontinuation of administration, increased to the pre-administration levels (p<0.05). Plasma renin activity and angiotensin I showed no significant changes throughout the administration study. These results provide experimental evidence that hypertension develops in dogs with chronic renal failure through mechanisms involving the RAA system and demonstrate that benazepril hydrochloride improves renal hypertension in dogs.

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.

Revisiting methods for assessing and comparing left ventricular diastolic stiffness: impact of relaxation, external forces, hypertrophy, and comparators

Understanding diastolic function mandates feasible and accurate methods to construct and compare the diastolic pressure (P)-volume (V) relationship (PVR). This study compared the relaxation-corrected single beat (RC-SB) to the multiple-beat (MB) (vena cava occlusion) method for constructing the diastolic PVR in 26 young normal or old hypertensive dogs before and after increases in afterload (phenylephrine) or acute volume expansion in the presence (n = 14) or absence (n = 12) of the pericardium. The PVR data were fit to P = alphae(beta x V). Derived stiffness indexes compared included the stiffness coefficient (beta), curve-fitting constant (alpha), and the end-diastolic volume (EDV) at 10, 20, or 30 mmHg [EDV(x) = ln(P(x)/alpha)/beta] to account for covariance in alpha and beta. In pericardium-intact young normal and old hypertensive dogs studied over varying afterloads, the MB and RC-SB PVR appeared identical. The beta (r = 0.62) and alpha (r = 0.69) derived from the RC-SB vs. MB PVR showed moderate correlation but poor agreement. In contrast, the EDV(10-30) derived from RC-SB vs. MB PVR showed excellent correlation (r = 0.97) and agreement. The uncorrected SB method underestimated stiffness. As expected, after acute volume expansion, the RC-SB PVR was shifted upward from the MB PVR (decreased EDV(10-30); P < 0.05) in the pericardium-intact but not pericardium-absent dogs. The RC-SB method can substitute for the MB technique in construction of PVR in the absence of acute volume expansion. The concordance between these two methods was poorly reflected by comparing the derived alpha and beta but apparent when using EDV(10-30), which provides information regarding the position of the PVR in a single number.

Revisiting Methods for Assessing and Comparing Left Ventricular Diastolic Stiffness

Background: Controversies over the pathophysiology of heart failure with preserved EF have renewed interest in characterization and comparison of LV diastolic stiffness, best assessed using the LV end-diastolic (ED) pressure (P)-volume (V) relationship obtained from multiple beats (MB) during rapid preload reduction. As the MB method is difficult, the diastolic P-V over a single beat with P corrected for effect of ongoing relaxation (RCSB) has been used in human studies but not validated against MB method. Further, the LV stiffness coefficient β in the relation EDP = αeβ∗EDV has been used to compare stiffness, but β covaries with α. This covariance is accounted for by comparing derived EDV at similar EDP, calculated from α, β and EDP of 10, 20 or 30 mmHg (EDV10-30). Objective: Determine if the RCSB method of assessing diastolic stiffness (as quantified by β or EDV10-30) shows good correlation and agreement with the MB method. Methods: P, V were invasively measured and the RCSB followed by MB methods performed in 26 young normal or elderly hypertensive dogs before and during phenylephrine (to vary afterload) or acute volume expansion. In the RCSB method, diastolic P was corrected by subtracting the P due to relaxation, monoexponentially extrapolated from isovolumic relaxation. Correlation was assessed by linear regression. Agreement was expressed as the mean ± SD of the paired difference between MB and RCSB values for β or EDV10-30, expressed as percentages of their mean values; p is for paired t-test. Results: Over widely varying afterloads (LV systolic P 95 to 236 mmHg), EDV10-30 derived from RCSB and MB methods showed excellent correlation (r = 0.98, p < 0.0001) and agreement (0.6 ± 5%, p = 0.6). Correlation (r = 0.62, p = 0.002) and agreement (4.2 ± 45%, p = 0.7) between β from SB and MB was poorer. Use of a limited number of P and V points for the RCSB method (at minimum LV P, pre-atrial contraction, and ED) resulted in less agreement between the methods in assessing EDV10-30 (4.4 ± 9%, p = 0.0003) or β (21 ± 40%, p = 0.025). Neither β (12.5 ± 55%, p = 0.5) nor EDV10-30 (10 ± 10%, p < 0.0001) derived from RCSB agreed with MB after marked volume expansion in presence of pericardium. Conclusion: Clinical studies seeking to compare diastolic stiffness between groups can use the clinically more feasible RCSB to substitute for the complex MB technique under a wide range of afterload. Accuracy will be influenced by the number of P and V points used and by presence of acute volume overload. Comparison of stiffness between groups will be enhanced by methods which account for the covariance between α and β.

Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence‐based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the ACVIM Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.

Total peripheral resistance responsiveness during the development of secondary renal hypertension in dogs

To determine whether the responses of total peripheral resistance and arterial pressure to vasoconstrictor agents are amplified as renovascular hypertension develops in dogs. After baseline measurements, the effects of renal artery stenosis (1K, 1C hypertension) were studied in groups of untreated and enalapril-treated dogs early (1-3 weeks) and later (4-6 weeks) as the hypertension developed. Both resting and open-loop haemodynamic measurements were made and the effects of acute intravenous infusions of vasopressin (0.25, 0.5 and 1.25 ng/kg per min) and phenylephrine (0.125, 0.25 and 0.50 microg/kg per min on arterial pressure, cardiac output and calculated total peripheral resistance responses were measured. Renal artery stenosis induced an increase in arterial blood pressure in both groups of dogs, with similar changes in haemodynamics also observed in open-loop conditions. The slopes of arterial pressure and peripheral resistance responses to vasopressin and phenylephrine were not significantly changed in early or late hypertension, in either the untreated or enalapril-treated groups. Hypertension from renal artery stenosis in dogs was due to nonautonomic, nonangiotensin II mechanisms. There was no evidence of vascular amplification of the effects of vasoconstrictor agents, indicating that this did not play a role in the development of hypertension.

Guidelines for the Identification, Evaluation, and Management of Systemic Hypertension in Dogs and Cats

Consensus Statements of the American College of Veterinary Internal Medicine (ACVIM) provide veterinarians with guidelines regarding the pathophysiology, diagnosis, or treatment of animal diseases. The foundation of the Consensus Statement is evidence-based medicine, but if such evidence is conflicting or lacking, the panel provides interpretive recommendations on the basis of their collective expertise. The Consensus Statement is intended to be a guide for veterinarians, but it is not a statement of standard of care or a substitute for clinical judgment. Topics of statements and panel members to draft the statements are selected by the Board of Regents with input from the general membership. A draft prepared and input from Diplomates is solicited at the ACVIM Forum and via the ACVIM Web site and incorporated in a final version. This Consensus Statement was approved by the Board of Regents of the ACVIM before publication.

Ligustilide Reduces Phenylephrine Induced-Aortic Tension In Vitro but has No Effect on Systolic Pressure in Spontaneously Hypertensive Rats

Radix Angelica sinensis, known as Danggui in Chinese, has been used to treat cardiovascular diseases in traditional Chinese medicine for a long time. Experimental evidence showed that the essential oil of Danggui could reduce blood pressure in rabbits, cats or hypertensive dogs when given intravenously. In this study, we investigated the effects of Z-ligustilide, the main lipophilic component of the essential oil of Danggui on aortic tension induced by phenylephrine, an alpha-adrenergic agonist, in vitro and the systolic blood pressure in SHR rats. We demonstrated for the first time that ligustilide can significantly reduce the phenylephrine-induced aortic tension in vitro with IC(50) about 64 mug/ml, but has no in vivo effect on systolic blood pressure in SHR rats when administrated orally. The data on transport of ligustilide across Caco-2 monolayer suggested an efficient intestinal absorption of ligustilide in vivo, implying that the non-effectiveness of ligustilide in vivo is not due to the poor absorption in the gastrointestinal tract. Further studies on whether ligustilide is one of the main anti-hypertensive components of the essential oil are needed.

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.

Accuracy of an oscillometric blood pressure monitor during phenylephrine-induced hypertension in dogs

To examine the agreement between direct arterial blood pressure measurements obtained from 2 arteries and indirect blood pressure measurements obtained with an oscillometric blood pressure monitor (OBPM) during normotension and phenylephrine-induced hypertension in dogs. 16 male Beagles. In anesthetized dogs, arterial catheters were placed in the lingual and dorsal pedal arteries for measurement of arterial blood pressure. A blood pressure cuff was placed on either the dog's fore- or hind limb and connected to an OBPM. Systolic, diastolic, and mean arterial blood pressures (SAP, DAP, and MAP, respectively) were recorded from both arteries and the OBPM every 5 minutes for 30 minutes (baseline), during a 30-minute period in which dogs received a phenylephrine infusion IV to induce hypertension, and for 30 minutes after discontinuation of the infusion. Mean differences in blood pressure values and confidence intervals were calculated to compare the indirect and direct measurement techniques. In dogs, oscillometry underestimated SAP during normotension, and the difference between oscillometric and direct measurements increased during hypertension. Oscillometry underestimated DAP, but the difference between oscillometric and direct measurements decreased during hypertension. There was close agreement among techniques for MAP determinations. Biases between direct measurements and OPBM blood pressure values measured from dogs' forelimbs or hind limbs were not significantly different. In normotensive dogs, oscillometric measurements of MAP and SAP agreed more closely with direct arterial pressure measurements than oscillometric estimates of DAP. Oscillometric measurement of MAP was accurate during both normotension and hypertension in dogs.

Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in Dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide‐mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPS) 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPS, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPS was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPS was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPS and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.

Systemic Hypertension in Dogs with Leishmaniasis: Prevalence and Clinical Consequences

A prospective study was performed (November 1998 to December 2003) to determine the prevalence of systemic hypertension (SH) in dogs with glomerular disease secondary to leishmaniasis. One hundred and five dogs with leishmaniasis were screened and staged for the presence of renal disease (RD) and SH. For the purpose of the study, RD was defined as serum creatinine concentration ≥ 1.4 mg/dL, a urine protein/creatinine ratio ≥ 0.5, or both. SH was defined as a systolic blood pressure (SBP) ≥ 180 mm Hg or an SBP between 150 and 179 mm Hg in the presence of clinical manifestations of SH. Fifty‐two (49.5%) of the dogs had some degree of RD, and 32 (61.5%) of these dogs were diagnosed with SH. Moreover, SH also was diagnosed in 3 dogs without RD. Left ventricular hypertrophy (LVH), estimated by echocardiography, was the most frequently observed systemic consequence of hypertension, being present in 32 (91.4%) of the hypertensive dogs. Echocardiographic abnormalities were not detected in any of the 33 dogs with leishmaniasis without RD, which were used as controls. Ocular consequences of SH were observed in only 2 (5.7%) of the dogs with hypertension. We conclude that SH is prevalent in dogs with RD secondary to leishmaniasis, not only in the more severe stages but also in the early course of the illness before azotemia becomes apparent. Canine leishmaniasis may be a useful natural model to study SH secondary to glomerular disease.

Systemic Hypertension in Dogs with Leishmaniasis: Prevalence and Clinical Consequences

A prospective study was performed (November 1998 to December 2003) to determine the prevalence of systemic hypertension (SH) in dogs with glomerular disease secondary to leishmaniasis. One hundred and five dogs with leishmaniasis were screened and staged for the presence of renal disease (RD) and SH. For the purpose of the study, RD was defined as serum creatinine concentration > or = 1.4 mg/dL, a urine protein/creatinine ratio > or = 0.5, or both. SH was defined as a systolic blood pressure (SBP) > or =180 mm Hg or an SBP between 150 and 179 mm Hg in the presence of clinical manifestations of SH. Fifty-two (49.5%) of the dogs had some degree of RD, and 32 (61.5%) of these dogs were diagnosed with SH. Moreover, SH also was diagnosed in 3 dogs without RD. Left ventricular hypertrophy (LVH), estimated by echocardiography, was the most frequently observed systemic consequence of hypertension, being present in 32 (91.4%) of the hypertensive dogs. Echocardiographic abnormalities were not detected in any of the 33 dogs with leishmaniasis without RD, which were used as controls. Ocular consequences of SH were observed in only 2 (5.7%) of the dogs with hypertension. We conclude that SH is prevalent in dogs with RD secondary to leishmaniasis, not only in the more severe stages but also in the early course of the illness before azotemia becomes apparent. Canine leishmaniasis may be a useful natural model to study SH secondary to glomerular disease.

The Effects of a Timolol Maleate Gel-Forming Solution on Normotensive Beagle Dogs

The effects of a timolol maleate gel-forming solution (TMGS) on intraocular pressure (IOP), blood pressure (BP), and pupil size (PS) were evaluated in normotensive dogs. TMGS was administered once daily to six normotensive beagle dogs. TMGS administration reduced IOP and PS. The hypotensive effect persisted for 24 hr after the administration. The mean reduction in IOP was 5.3 mm Hg (P<0.01). The changes in BP and PS were not significant. These results suggest that TMGS can potentially be used in the treatments of glaucoma and ocular hypertension in dogs.

Retrospective Evaluation of Sildenafil Citrate as a Therapy for Pulmonary Hypertension in Dogs

Pulmonary arterial hypertension (PH) is a pathologic condition in dogs characterized by abnormally high pressures in the pulmonary circulation and has been associated with a poor outcome. Sildenafil is a type V phosphodiesterase inhibitor that produces nitric oxide mediated vasodilatation. Sildenafil treatment decreases pulmonary arterial pressure and pulmonary vascular resistance in people with PH. The purpose of this study was to describe the clinical characteristics and outcome of dogs with PH treated with sildenafil. The cardiology database was searched for dogs with PH treated with sildenafil. PH was defined as systolic pulmonary arterial pressure (PAPs) > or = 25 mmHg at rest. Medical records were reviewed for the following information: signalment, duration and type of clinical signs before treatment, underlying disease, estimated or measured PAPs, dosage and dosing interval of sildenafil, and the effect of treatment on clinical signs and pulmonary arterial pressure and survival time. Thirteen affected dogs were identified. Clinical signs included collapse, syncope, respiratory distress, and cough. Duration of clinical signs before presentation ranged from 3 days to 5 months. An underlying cause was identified in 8 dogs. The median sildenafil dosage was 1.9 mg/kg. Ten dogs received concurrent medications. Median PAPs was 90 mmHg; 8 dogs were reevaluated after therapy, and the median decrease in PAPs was 16.5 mmHg. The median survival time of all dogs was 91 days. Sildenafil appeared to be well tolerated in dogs with PH and was associated with decreased PAPs and amelioration of clinical signs in most. Sildenafil represents a reasonable treatment option for dogs with pulmonary hypertension.

The role of spleno-pulmonary parenchymatous anastomosis in the reduction of portal hypertension in dogs.

The role of spleno-pulmonary parenchymatous anastomosis in the reduction of portal hypertension in dogs.

Pharmacokinetic and Pharmacodynamic Interaction Between Irbesartan and Hydrochlorothiazide in Renal Hypertensive Dogs

Combined irbesartan/hydrochlorothiazide (HCTZ) formulations are often used clinically. Pharmacokinetic-pharmacodynamic (PK/PD) modeling was applied to investigate the pharmacokinetic and pharmacodynamic interaction between irbesartan and HCTZ in renal hypertensive dogs at non-steady-state and steady-state. The renal hypertensive dogs were treated with oral irbesartan alone, or HCTZ alone, or the combination of irbesartan and HCTZ for 8 days. Blood pressure and plasma concentrations were measured and pharmacokinetic-pharmacodynamic parameters were analyzed. Irbesartan showed a two-compartment model pharmacokinetic profile. The concentration-time course of irbesartan was not changed by HCTZ, but irbesartan increased the peak plasma concentration and area under the curve of HCTZ at steady-state. HCTZ had no blood pressure lowering effect at non-steady-state. Irbesartan plus HCTZ had greater blood pressure lowering action than irbesartan alone. HCTZ increased actions of irbesartan. Hysteresis loops were found between effect and plasma concentrations of irbesartan after a single dose. However, hysteresis loops disappeared at steady state with more rapid realization of maximum concentration and effects. The relationship between effects and effect-compartment concentrations of the drugs was represented by a sigmoid Emax model. The results suggest synergistic pharmacodynamic interaction between irbesartan and HCTZ in renal hypertensive dogs and some differences of pharmacokinetic-pharmacodynamic properties between irbesartan and irbesartan/HCTZ combinations at non-steady-state and steady state.