Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients.
BACKGROUND
Essential hypertension is characterized by impaired endothelium-dependent vasodilation. The present study was designed to investigate whether this abnormality is a primary defect or a consequence of blood pressure increases.


RESULTS
In offspring of essential hypertensive patients (n = 34) and normotensive subjects (n = 30), we evaluated forearm blood flow (strain-gauge plethysmography) modifications induced by intrabrachial acetylcholine (0.15, 0.45, 1.5, 4.5, and 15 micrograms.100 mL-1.min-1), an endothelium-dependent vasodilator, and sodium nitroprusside (1, 2, and 4 micrograms.100 mL-1.min-1), an endothelium-independent vasodilator. Minimal forearm vascular resistances also were calculated as the ratio between mean intra-arterial pressure and maximal forearm blood flow induced by forearm ischemia and hand exercise. Vasodilation to acetylcholine was significantly (P < .01) blunted in offspring of hypertensive patients compared with offspring of normotensive subjects, whereas the responses to sodium nitroprusside and minimal forearm vascular resistances were similar. In two subgroups of 14 offspring of essential hypertensive patients but not in 10 offspring of normotensive subjects, vasodilation to acetylcholine was increased by intra-brachial L-arginine (1 mumol.100 mL-1.min-1), the substrate for nitric oxide synthesis, whereas in the other 10 and 8 offspring of essential hypertensive patients and normotensive subjects, respectively, cyclooxygenase blockade by intra-brachial indomethacin (50 micrograms.100 mL-1.min-1) was ineffective.


CONCLUSIONS
Offspring of essential hypertensive patients are characterized by a reduced response to acetylcholine linked to a defect in the nitric oxide pathway, suggesting that an impairment in nitric oxide production precedes the onset of essential hypertension.
Taddei
S
S
I Clinica Medica, University of Pisa, Italy.
Virdis
A
A
Mattei
P
P
Ghiadoni
L
L
Sudano
I
I
Salvetti
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001120:Arginine / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D012016:Reference Values; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D007213:Indomethacin