The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) effects of subcutaneous (SC) ALN-AGT01 (zilebesiran) in participants with hypertension. The study will be conducted in 4 parts: Part A will be a single ascending dose (SAD) phase in hypertensive participants, Part B will be a single dose (SD) phase in hypertensive participants with controlled salt intake, Part D will be a MD phase in hypertensive participants who are obese, and Part E will be an open-label SD phase with co-administration of irbesartan in hypertensive patients.
Inclusion Criteria: * Has mild to moderate hypertension with mean sitting systolic blood pressure (SBP) of \>130 and ≤165 mmHg without hypertensive medication for Parts A, B and D, and \>135 and ≤165 mmHg without hypertensive medication for Part E * Parts A and B: Has body mass index (BMI) ≥18 and ≤35 kg/m\^2; Part D: Has BMI \>35 and ≤50 kg/m\^2; Part E: Has BMI ≥18 kg/m\^2 and ≤50 kg/m\^2 * Has a normal 12-lead electrocardiogram (ECG) * Is a nonsmoker Exclusion Criteria: * Has secondary hypertension * Has orthostatic hypotension * Has estimated glomerular filtration rate (eGFR) of \<60 mL/min/1.73m\^2 * Recently received an investigational agent * Has diabetes mellitus * Has history of any cardiovascular event * Has history of intolerance to SC injection(s)