Synthesis of collagen in cardiac and vascular walls.

Collagen synthesis and content have been shown to be elevated in the arterial wall and heart of hypertensive animals. These increases in collagen synthesis and content have been implicated in the maintenance of raised blood pressure. Inhibitors of collagen synthesis, beta APN and 3,4-dihydroproline, were shown to delay the onset of hypertension and reverse established hypertension. Therapeutic intervention with antihypertensive drugs resulted in a decrease in arterial collagen synthesis and a reversal of cardiac hypertrophy. In some instances (i.e., DOCA-salt), chronic administration of antihypertensive drugs caused a restructuring of the arterial wall and resulted in an apparent remission of the hypertensive disease.

[Pathogenetic, pathophysiological and biochemical aspects of essential hypertension (author's transl)]. / Aspekte zur Pathogenese, Pathophysiologie und Pathobiochemie der essentiellen Hypertonie.

Hereditary and environmental factors are involved in the pathogenesis of essential hypertension. Obesity, salt intake and stress are predominant among the environmental influences. Autonomous nervous dysfunction, increased contractility of vascular smooth muscle cells and impaired renal handling of sodium are major abnormalities in essential hypertension. At present it cannot be decided if alterations in the activities of systemic or renal hormonal systems reflect primary defects or adaptive changes in the regulation of blood pressure. In any case the kidney is regarded to have a key position in the long term increase of blood pressure in essential hypertension. Recent studies in essential hypertensive patients suggest that renin release decreases as renal vascular resistance increases. Studies from our laboratory have shown that renal prostaglandins are intrinsic to the renin release mechanism from the kidney. Additionally, there is evidence that renal prostaglandin synthesis is disturbed in essential hypertension, either primarily or secondarily, leading to unresponsive renin secretion. Further studies on the interrelationships of other hormonal systems and on hormone-receptor interactions in the vascular wall are necessary to delineate more precisely the mechanisms which are operative in the pathogenesis and manifestation of essential hypertension.