The renin-angiotensin-aldosterone system is stimulated significantly more in hypertensive patients with polycystic kidney disease than in comparable patients with essential hypertension.
To study whether changes in alpha- and beta-adrenoceptors in human essential hypertension (EHT) might be genetically determined, we assessed platelet alpha 2- and lymphocyte beta 2-adrenoceptor density in 48 normotensive children of normotensive parents (NT) and in 41 normotensive children with one EHT-parent.
Because renin is an important enzyme in blood pressure regulation, we studied the possibility that an alteration in the structure of the human renin gene is genetically linked to human essential hypertension or associated with levels of plasma renin activity or blood pressure.
We have previously described a subset of subjects with essential hypertension who fail to appropriately modulate renal vascular and adrenal reactivity with changes in dietary sodium and in response to infused angiotensin II (Ang II).
These findings suggest that, in addition to the known cardiovascular abnormalities of sympathetic, renal and ion transport mechanisms, a fourth area of disturbance involving the response of plasma aldosterone to Ang II may be present in normotensive subjects with familial predisposition to essential hypertension.
These findings suggest that, in addition to the known cardiovascular abnormalities of sympathetic, renal and ion transport mechanisms, a fourth area of disturbance involving the response of plasma aldosterone to Ang II may be present in normotensive subjects with familial predisposition to essential hypertension.
These observations are consistent with a potassium-remediable disturbance in NE- but not AII-dependent regulation of BP in the pathogenesis of essential hypertension.
The association between the C3F-gene and essential hypertension was stronger among the untreated patients, where a relative risk of 3.89 was found for C3F-positive subjects.5.
Vascular responses to endothelin-1 have been shown to be normal or depressed in many models of experimental hypertension, and also in humans with essential hypertension.
To determine whether the endothelial nitric oxide synthase gene is involved in human essential hypertension, we identified informative biallelic and multiallelic markers of this locus and performed case-control and linkage studies in hypertensive subjects and normotensive control subjects.
We concluded that essential hypertension as a multifactorial and heterogeneous disease cannot be associated with one of the HLA class II DRB and DPB1 alleles in Belgian patients.
To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain.
To date, mutations in three genes have been implicated in the pathogenesis of human hypertension: mutations resulting in ectopic expression of aldosterone synthase enzymatic activity cause a mendelian form of hypertension known as glucocorticoid-remediable aldosteronism; mutations in the beta subunit of the amiloride-sensitive epithelial sodium channel cause constitutive activation of this channel and the mendelian form of hypertension known as Liddle syndrome; finally, common variants at the angiotensinogen locus have been implicated in the pathogenesis of essential hypertension in Caucasian subjects, although the nature of the functional variants and their mechanism of action remain uncertain.
These findings provide support for linkage and association of the angiotensinogen locus to hypertension in African Caribbeans and suggest some similarities in the genetic basis of essential hypertension in populations of different ethnicity.
These results suggest that the contribution of variation in the angiotensinogen gene to the occurrence of essential hypertension is less than initially suspected, or may not be constant across populations.
In a separate study, the T235 homozygote of the angiotensinogen gene was associated with the non-modulating intermediate phenotype of essential hypertension.