Prenatal and Postnatal Hydralazine Treatment Does Not Prevent Renal Vessel Wall Thickening in SHR Despite the Absence of Hypertension

• Published in: Circulation research 1988-09, Vol.63 (3), p.534-542
• Main Authors: Smeda, John S, Lee, Robert M.K.W, Forrest, James B
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn - anatomy & histology; Animals, Newborn - physiology; Antihypertensive agents; Biological and medical sciences; Blood Pressure - drug effects; Blood Vessels - pathology; Cardiovascular system; Female; Hydralazine - pharmacology; Medical sciences; Muscle, Smooth, Vascular - anatomy & histology; Muscle, Smooth, Vascular - drug effects; Pharmacology. Drug treatments; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Inbred SHR - anatomy & histology; Rats, Inbred SHR - physiology; Rats, Inbred Strains - anatomy & histology; Rats, Inbred WKY; Renal Artery - anatomy & histology; Renal Artery - drug effects; Renal Circulation - drug effects; Substance Withdrawal Syndrome - physiopathology; Systole
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/01.RES.63.3.534

Previous studies in our laboratory have shown that the renal blood vessels of 21-week-old Wistar-Kyoto spontaneously hypertensive rats exhibited thicker vascular walls than age matched Wistar-Kyoto normotensive rats. Morphometric analysis of the relaxed renovasculature revealed an increase in the cross-sectional area of the media, which in most cases was associated with an increase in the number of smooth muscle cell layers. To test if these structural changes occur in the absence of raised blood pressure, hydralazine was administered to spontaneously hypertensive rats and normotensive controls prior to and during pregnancy (100 ml/1 drinking water), and to the newborn males up to 21 weeks of age (16.9 mg/kg/day by gavage until weaning followed by 100 mg/1 in the drinking water). Treated animals were compared with untreated rats. Treatment prevented hypertension development in spontaneously hypertensive rats but did not alter the structural changes found in untreated animals with hypertension. At 21 weeks of age, hydralazine-treated spontaneously hypertensive rats had similar wall-to-lumen area ratios, medial cross-sectional areas and numbers of medial smooth muscle layers as untreated hypertensive rats while these parameters were greater in treated and untreated spontaneously hypertensive rats than in either treated or untreated normotensive controls. Withdrawal of hydralazine from 26-week-old spontaneously hypertensive rats that had been treated in utero and postnatally and had normal blood pressures throughout life resulted in the rapid onset of hypertension. Our results show that renal vascular wall thickening in spontaneously hypertensive rats occurs in the absence of high blood pressure and therefore is not a secondary effect of raised blood pressure.