Variability in Adrenergic Response

The dorsal hand vein model is a relatively non-invasive and robust experimental model to
examine the local in vivo effect of vasoactive drugs without elucidating systemic
counterregulatory reflexes. Infusion of incremental low doses of phenylephrine into a dorsal
hand vein results in increasing local venoconstriction, without systemic effects. Similarly,
infusion of incremental low doses of nitroglycerin into a preconstricted dorsal hand vein
results in increasing local venodilation, without systemic effects. Systemic vascular
responses can be measured by the cold pressor test (CPT),that leads to increase in blood
pressure and heart rate , or mental stress that is also known to stimulate cardiovascular
responses. Individuals vary in their local and systemic vascular responses but the genetic
determinants of these are not clear.

Inclusion Criteria:

- Age between 18 and 40 years, inclusive.

- Subject must be willing to give written informed consent and be able to adhere to diet
and study schedules.

- Subjects must be free of any clinically significant disease that requires a
physician's care and/or would interfere with the study evaluations.

- Subjects must have a normal or clinically acceptable physical examination and ECG.

- Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within
normal limits or clinically acceptable to the investigator.

Exclusion Criteria:

- Any subject who has taken any prescription or over-the-counter drugs, other than oral
contraception if female, within two weeks prior to study drug administration.

- Subjects who are presently, or were formerly, narcotic addicts or alcoholics.

- Subjects who have a clinically significant allergy/intolerance to phenylephrine.

- Females with a positive serum/urine pregnancy test at screening.

- Females who are nursing.

- Subject using sildenafil or other phosphodiesterase inhibitors.