Drugs online research references
J Cardiovasc Pharmacol. 1987;10 Suppl 7:S141-4.
CE inhibition and natriuresis with ramipril in conscious SHR: different modes of action of loop and thiazide diuretics.
Becker RH, Baldes L, Treudler M.
Hoechst AG, Frankfurt, F.R.G.
Acute effects of piretanide, a loop diuretic, on blood pressure (BP) and urinary output as well as long-term effects on serum electrolytes were compared in conscious spontaneously hypertensive rats (SHR) to that of hydrochlorothiazide (HCT) both given alone and in combination with the converting enzyme (CE) inhibitor ramipril. There were no acute or chronic falls in BP with low doses of either diuretic. Ramipril at a dose of 10 mg/kg normalized BP, which was accompanied by initial natriuresis and, over the long term, K+ preservation. Minimally effective doses of piretanide but not HCT given in combination with 1 mg/kg ramipril produced a greater fall in BP both acutely and chronically than ramipril alone at unaltered K+ preservation. To match this fall in BP with HCT, large doses were required, which caused hemoconcentration and impaired K+ preservation.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2485050&dopt=Abstract
Hypertension. 1999 Jun;33(6):1342-7.
Variable renal atrial natriuretic factor gene expression in hypertension.
Ogawa T, Linz W, Scholkens BA, de Bold AJ.
University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
We have previously established the existence of atrial natriuretic factor (ANF) gene expression within the renal parenchyma. Neither the role nor the regulation of this extracardiac source of ANF is clearly defined. To determine whether renal ANF gene expression, similar to cardiac expression, is linked to the activity of the renin-angiotensin system (RAS), we compared renal ANF gene expression in rats after suprarenal aortic banding, a hypertension model associated with activation of RAS, and in the deoxycorticosterone acetate (DOCA)-salt model, which is characterized by depression of RAS. Renal ANF mRNA was measured with a quantitative competitive reverse transcription polymerase chain reaction method. DOCA-salt hypertension significantly reduced the expression of renal ANF. In contrast, aortic banding significantly increased renal ANF expression. In both cases, ANF gene expression in the heart increased. Ramipril treatment at 10 micrograms/kg of aortic-banded rats, a treatment that specifically affects local RAS but maintains hypertension, normalized renal ANF mRNA levels. Altogether, these results suggest that renal ANF gene expression is modulated by local RAS and is independent of circulating RAS and hypertension per se. The marked decrease of renal ANF mRNA in DOCA-salt hypertension suggests a pathogenic role for renal ANF gene downregulation by decreasing the sodium excretory mechanism mediated by the local expression of ANF acting on receptors found in the inner medullary collecting ducts. In aortic banding, renal ANF gene expression upregulation suggests a local compensatory function consistent with the consensus role of natriuretic peptides in the modulation of RAS, thus ameliorating the sodium-retaining effects of renal underperfusion.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10373213&dopt=Abstract
Am J Cardiol. 1987 Apr 24;59(10):92D-97D.
Blood pressure response of nephrectomized subjects and patients with essential hypertension to ramipril: indirect evidence that inhibition of tissue angiotensin converting enzyme is important.
Wenting GJ, Blankestijn PJ, Poldermans D, van Geelen J, Derkx FH, Man in't Veld AJ, Schalekamp MA.
The kinetics of blood pressure changes and plasma angiotensin converting enzyme (ACE) inhibition in response to ramipril (HOE 498), 10 mg orally, were studied in 6 nephrectomized subjects 12 hours after ultrafiltration and in 10 patients with essential hypertension. Ramipril lowered supine and standing blood pressure in both groups, but the effect was greater in essential hypertension. The maximal blood pressure response followed the effect on plasma ACE after a lag time of 3 to 4 hours in both groups. These data provide indirect evidence that ramipril lowers blood pressure, at least in part, independently of its effect on the circulating renin-angiotensin system, possibly by acting on tissue ACE.
online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3034041&dopt=Abstract
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