Studies of vascular dna synthesis during the development of hypertension.
thesisposted on 19.11.2015, 08:50 by Joanne Susan. Lymn
Medial hypertrophy of arteries and resistance vessels is a consistent feature of hypertension although its relationship to the rise in blood pressure remains unclear. Previous studies can generally be divided into morphological studies of resistance arteries, detecting only the end product of structural change, or biochemical studies of large conduit vessels which do not regulate peripheral vascular resistance. In this study I have monitored the changes in blood pressure, rate of DNA synthesis, protein content and DNA content of large vessels and small resistance arteries from rats with developing two-kidney, one-clip Goldblatt (2K, 1C) and genetic (SH) hypertension. At three days post-2K, 1C a significant increase in [3H] - thymidine incorporation was observed although blood pressure remained unchanged. By 28 days DNA synthesis had returned to control levels while blood pressure remained elevated. A significant rise in protein content was detected in the aorta and in the mesenteric arteries where DNA content was also elevated. No change in DNA/protein ratio was detected. In contrast the rate of DNA synthesis of vessels from SH rats did not differ from control values at any age. At 18 weeks the aortic protein content was increased with a corresponding decrease in DNA/protein ratio. The protein and DNA content of the resistance vessels remained unchanged. It would appear that the changes which lead to structural modifications in 2K, 1C hypertension begin before any significant rise in blood pressure, and that the medial hypertrophy can be attributed to cellular hypertrophy in the aorta and hyperplasia in the mesenteric arteries. However, structural modification in the SH rat appears to depend on mechanisms which do not involve amplification of DNA synthesis in postnatal life.