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ECKART SCHOTT, MARTIN PAUL AND DETLEV GANTEN
excretion indicating that the adrenal glands aremoresensitive to ACTHstimulation in this transgenic line. Since spironolactone treatment did not
reduce blood pressure in these animals, hypertensionwas probably not due
to excess of mineralocorticoids. Hilgers et al. (49) demonstrated that the
vasculature of the transgenic animals produced increased amounts of
ANG II, which was most likely the result of overexpression of the transgene
in the vascular wall. This observationwas proved by a sensitive RNase protection assay (49).
The hearts of these transgenic animals showed pathological changes such
as hypertrophy and fibrosis (50), which only in part were explained by altered blood pressure Ievels. Current studies, therefore, focus on the investigation of additional effects on cardiac function in these animals.
Other models in transgenic hypertension research include mice and rats
expressing human renin (51, 52) or human angiotensinogen (1, 53, 54).
These approaches suggest that products of endogenous genes and transgenes do not interact at the measured concentrations. The results from Coexpression of the human transgenes in crossbred transgenic animals carrying both genes in one organ supports the possibility of local angiotensin I
production from the interaction of the human proteins. The functional role
of such human-dependent, tissue-specific RAS remains tobe established.
Other recent approaches include development of transgenic mice expressing atrial natriuretic peptide (ANP), resulting in a decrease in
mean arterial pressure of 20-30 mmHg (3), and the development of mice
that are transgenic for rat arginine-vasopressin (A VP), resulting in mice
suffering from SiADH (55, 56). An interesting modelwas established by
Hofmann et al. (57) who generated a transgenic mouse, expressing the
gene encoding the human LDL receptor driven by the mouse metallothionein promoter. Afteradministration of cadmium, these animals cleared intravenously-injected 125 1-labeled LDL from blood eight toten times more
rapidly than did normal control mice. This protocol may Iead to interesting
clinical applications in patients who suffer from congenital LDL receptor
deficiency that predisposes to the development of artherosclerosis.
Other candidate genes for the development of transgenic animals in hypertension research are the genes encoding human heart chymase and
genes of the endothelin family (58).
ECKART SCHOTT, MARTIN PAUL AND DETLEV GANTEN
excretion indicating that the adrenal glands aremoresensitive to ACTHstimulation in this transgenic line. Since spironolactone treatment did not
reduce blood pressure in these animals, hypertensionwas probably not due
to excess of mineralocorticoids. Hilgers et al. (49) demonstrated that the
vasculature of the transgenic animals produced increased amounts of
ANG II, which was most likely the result of overexpression of the transgene
in the vascular wall. This observationwas proved by a sensitive RNase protection assay (49).
The hearts of these transgenic animals showed pathological changes such
as hypertrophy and fibrosis (50), which only in part were explained by altered blood pressure Ievels. Current studies, therefore, focus on the investigation of additional effects on cardiac function in these animals.
Other models in transgenic hypertension research include mice and rats
expressing human renin (51, 52) or human angiotensinogen (1, 53, 54).
These approaches suggest that products of endogenous genes and transgenes do not interact at the measured concentrations. The results from Coexpression of the human transgenes in crossbred transgenic animals carrying both genes in one organ supports the possibility of local angiotensin I
production from the interaction of the human proteins. The functional role
of such human-dependent, tissue-specific RAS remains tobe established.
Other recent approaches include development of transgenic mice expressing atrial natriuretic peptide (ANP), resulting in a decrease in
mean arterial pressure of 20-30 mmHg (3), and the development of mice
that are transgenic for rat arginine-vasopressin (A VP), resulting in mice
suffering from SiADH (55, 56). An interesting modelwas established by
Hofmann et al. (57) who generated a transgenic mouse, expressing the
gene encoding the human LDL receptor driven by the mouse metallothionein promoter. Afteradministration of cadmium, these animals cleared intravenously-injected 125 1-labeled LDL from blood eight toten times more
rapidly than did normal control mice. This protocol may Iead to interesting
clinical applications in patients who suffer from congenital LDL receptor
deficiency that predisposes to the development of artherosclerosis.
Other candidate genes for the development of transgenic animals in hypertension research are the genes encoding human heart chymase and
genes of the endothelin family (58).