ramipril and Cerebrovascular-Disorders

The use of the cardiovascular polypill, a fixed-dose combination treatment, is conceived to improve adherence. However, randomized controlled trials (RCTs) may overestimate it. Studies focusing on cerebrovascular disease and real-life efficacy compared with conventional treatment are lacking.. This is a retrospective, hospital-based cohort study of acute ischaemic stroke patients who were prescribed a polypill (aspirin 100 mg, atorvastatin 20/40 mg, ramipril 2.5/5/10 mg) versus conventional treatment (aspirin 100 mg and other blood pressure/lipid-lowering agents) in secondary prevention (2017-2018). Clinical records were reviewed 90 days after discharge for stroke recurrence, vascular risk factor control, and safety. Adherence was assessed using the adapted Morisky-Green scale.. A total of 104 patients were included (61% male; mean age 69.7 ± 13.9 years); 54 were treated with the polypill and 50 with conventional treatment. No baseline differences in clinical or demographic variables were detected. No recurrences were registered in the polypill group, compared to 1 recurrence in the conventional treatment group. A significant reduction of systolic blood pressure (SBP) was achieved in the polypill group (12.1 mm Hg) compared to the conventional treatment group (6.8 mm Hg) (p = 0.002). No significant differences were detected regarding the goal of LDL cholesterol ≤70 mg/dL (41 vs. 44%). The adverse events were mild and their frequency was similar in the two groups (9 vs. 2%, ns). Adherence was similarly good in the two groups (93 vs. 88%, ns). Polypill group adherence was similar to that reported in a previous meta-analysis of RCTs (93 vs. 84%, ns).. In our experience, the cardiovascular polypill achieved a higher reduction in SBP levels and was well tolerated. Adherence was similar to that found in the previous literature, which is remarkable given the real-life setting of our study.

Topics: Administration, Oral; Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Aspirin; Atorvastatin; Cerebrovascular Disorders; Drug Combinations; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Medication Adherence; Middle Aged; Platelet Aggregation Inhibitors; Ramipril; Recurrence; Retrospective Studies; Secondary Prevention; Tablets; Tertiary Care Centers; Time Factors; Treatment Outcome

The effect of life-long treatment with the ACE inhibitor ramipril on hypertension-induced histological changes in the kidney was tested in stroke-prone spontaneously hypertensive rats (SHR-SP).. One-month-old pre-hypertensive SHR-SP were randomized into three groups of 45 animals each, and exposed via drinking water for their lifetime to a dose of: 1 mg.kg-1.d-1 ramipril (antihypertensive dose, HRA); 10 micrograms.kg-1.d-1 slight dose of ramipril (non-antihypertensive dose, LRA); or placebo. Histological and biochemical assessments were conducted after 15 months in ten rats each, when about 80% of the placebo group had died.. Kidneys from placebo treated SHR-SP showed pronounced arterial wall hypertrophy and sclerosis, arterial fibrinoid necrosis, glomerulopathy and tubular interstitial injury that were, in concert with normalized blood pressure, completely prevented by HRA treatment. LRA treatment did not affect any blood pressure increase, and also attenuated the development of arterial wall hypertrophy, sclerosis and arterial fibrinoid necrosis, though to a minor extent only, but did not change glomerular and tubulointerstitial degeneration. These effects of ramipril were associated with a dose-dependent inhibition of plasma and renal tissue ACE activities as well as lower serum concentrations of creatinine, but there were no changes in serum potassium.. Life-long HRA-induced ACE inhibition protects against hypertension-induced renal damages in SHR-SP. This is associated with a doubling of the lifespan in these animals.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Vessels; Cerebrovascular Disorders; Dose-Response Relationship, Drug; Genetic Predisposition to Disease; Hypertension, Malignant; Hypertrophy; Kidney; Male; Necrosis; Ramipril; Rats; Rats, Inbred SHR; Time Factors

1. The influence of salt (sodium chloride; NaCl) (an additional 6% in the diet) and that of a novel sodium-reduced, potassium-, magnesium-, and L-lysine-enriched salt alternative on the cardiovascular effects of ramipril was studied in stroke-prone spontaneously hypertensive rats in a 6-week study. The intake of sodium chloride was adjusted to the same level by adding the salt alternative at a 1.75 times higher amount than regular salt. 2. Salt produced a marked rise in blood pressure and induced cardiac hypertrophy and significant mortality, while the salt alternative neither increased blood pressure nor caused any mortality and produced less cardiac hypertrophy than salt. 3. Ramipril treatment at a daily dose of 3 mg kg-1 normalized blood pressure and prevented the development of cardiac hypertrophy of rats on control diet. These effects of ramipril were blocked by the addition of salt but were only slightly attenuated by the addition of the salt alternative. The mortality in the salt group was prevented by ramipril. 4. Responses of mesenteric arterial rings in vitro were examined at the end of the study. Salt, but not the salt alternative, increased vascular contractile responses to noradrenaline. Ramipril treatment improved the arterial relaxation responses to acetylcholine and to sodium nitroprusside. The vascular relaxation enhancing effect of ramipril was blocked by salt but only slightly attenuated by the salt alternative. 5. Ramipril treatment did not significantly increase plasma renin activity in the presence or in the absence of salt supplementation. The salt alternative did not cause hyperkalaemia, either alone or in combination with ramipril treatment. 6. Both salt supplementations, irrespective of ramipril treatment, induced a six to eight fold increase in the urinary excretion of calcium. There was an expected 90 to 140% rise in the urinary excretion of magnesium and 200% rise in the urinary excretion of potassium in the salt alternative group. Salt also produced an approximately 50% increase in magnesuria.7. Our findings suggest that replacement of salt by the potassium-, magnesium- and L-lysine-enriched salt alternative improves the cardiovascular effects of ramipril. In the present study the beneficial effect was related to the increased intakes of potassium and/or magnesium and L-lysine from the salt alternative because the amount of sodium chloride was the same.

Topics: Animals; Blood Pressure; Cardiovascular System; Cerebrovascular Disorders; Electrolytes; Hypertrophy, Left Ventricular; Magnesium; Male; Mesenteric Arteries; Potassium; Ramipril; Rats; Rats, Inbred SHR; Sodium Chloride

The effect of chronic low- and high-dose treatment with the angiotensin-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenatally and subsequently up to the age of 20 weeks. The contribution of endogenous bradykinin potentiation to the ACE inhibitor actions was assessed by cotreatment of rats with the bradykinin B2-receptor antagonist Hoe 140 (500 micrograms/kg per day SC) from 6 to 20 weeks of age. High- but not low-dose ACE inhibitor treatment prevented the development of hypertension and left ventricular hypertrophy. Chronic bradykinin receptor blockade did not attenuate the antihypertensive and antihypertrophic actions of ramipril. High-dose ramipril treatment improved cardiac function, as demonstrated by an increase in left ventricular pressure (29.9%), dP/dtmax (34.9%), and coronary flow (22.1%), without a change in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentrations of glycogen and the energy-rich phosphates ATP and creatine phosphate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatment led to a pattern of changes in cardiodynamics and cardiac metabolism similar to that observed with the high dose. All ACE inhibitor-induced effects on cardiac function and metabolism were abolished by chronic bradykinin receptor blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Administration, Oral; Animals; Bradykinin; Cerebrovascular Disorders; Coronary Circulation; Creatine Kinase; Dose-Response Relationship, Drug; Female; Glycogen; Heart; Hypertension; Hypertrophy, Left Ventricular; L-Lactate Dehydrogenase; Lactates; Male; Myocardium; Phosphocreatine; Pregnancy; Ramipril; Rats; Rats, Inbred SHR; Rats, Wistar; Ventricular Pressure

Recent studies indicate that norepinephrine-induced contractile oscillations in the tail artery from stroke-prone spontaneously hypertensive rats (SHRSP) may be a vascular phenomenon independent of blood pressure level. The objectives of this study were: (1) to characterize pharmacologically the alpha-adrenoceptor mediating norepinephrine-induced oscillations in tail artery; and (2) to investigate the relationship between blood pressure level, altered by treatments with hydralazine/hydrochlorothiazide or the angiotensin converting enzyme inhibitor ramipril, and the observation of norepinephrine-induced oscillations in tail artery. The alpha 2-adrenoceptor agonists clonidine and guanabenz potently stimulated oscillatory contractions in the tail artery while the alpha 1-adrenoceptor agonists phenylephrine and methoxamine were considerably less potent. Yohimbine, an alpha 2-adrenoceptor antagonist, but not the alpha 1-adrenoceptor antagonist prazosin demonstrated high affinity for the receptor mediating norepinephrine-induced oscillatory contractions. These results support the hypothesis that norepinephrine-induced oscillatory contractions in the tail artery from SHRSP occur primarily through stimulation of alpha 2-adrenoceptors. Ramipril lowered blood pressure in SHRSP after 4 weeks of treatment during 6-10 weeks of life but did not alter the ability of the alpha 2-adrenoceptor agonist clonidine (10(-5) M) to induce contractile oscillations in tail arteries from SHRSP, indicating these oscillations are not a secondary effect of high blood pressure. These studies suggest that norepinephrine-induced oscillations in tail artery from SHRSP may be a vascular trait separate and distinct from blood pressure level and angiotensin II expression early in life.

Topics: Animals; Arteries; Blood Pressure; Cerebrovascular Disorders; Disease Susceptibility; Hypertension; Muscle, Smooth, Vascular; Norepinephrine; Periodicity; Ramipril; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, Adrenergic, alpha; Tail; Vasoconstriction