Long-term effects of early administered sildenafil and NO donor on the cardiovascular system of SHR.
We evaluated the long-term effect of NO-donor, pentaerythrityl tetranitrate (Petn), and sildenafil citrate (sildenafil) on the cardiovascular system of the spontaneously hypertensive rat (SHR). Petn (100 mg/kg/day) and sildenafil (10 mg/kg/day) were administered to SHR individually or together from week 4 (pre-hypertensive period) to week 9 of age. Blood pressure (BP) was measured using a plethysmographic method. The animals were perfused with a glutaraldehyde fixative (120 mmHg). Carotid (AC) and coronary artery (RS) were processed according to electron microscopy procedure. Geometry of the arteries was measured on semi-thin sections using light microscopy. Administration of Petn and sildenafil to SHR individually or together did not prevent an increase of BP, but evoked a decrease of cardiac hypertrophy. Petn and sildenafil affected the geometry of RS and AC differently. In the RS, an increase of inner diameter (ID) without an increase of wall thickness (WT) resulted in increased WT/ID and circumferential stress. In the AC, changes in ID were accompanied by changes in WT and, thereby, WT/ID and circumferential stress remained unchanged. The arterial wall mass of both arteries was increased. The data suggest that administration of the NO donor, Petn, and/or sildenafil does not result in a beneficial effect on the myocardium or on the geometry of the carotid and coronary arteries.
Kristek
F
F
Institute of Normal and Pathological Physiology, Slovak Academy of Aciences, Bratislava, Slovak Republic. Frantisek.kristek@savba.sk
Koprdová
R
R
Cebová
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002319:Cardiovascular System / Q000187:drug effects*; D002339:Carotid Arteries / Q000187:drug effects / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D010417:Pentaerythritol Tetranitrate / Q000008:administration & dosage; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011687:Purines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D000959:Antihypertensive Agents; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D000068677:Sildenafil Citrate