A Study to Assess the Safety, Tolerability and Efficacy of IONIS-AGT-LRx

Inclusion criteria: * Males or females aged 18-75 inclusive and weighing ≥ 50 kilograms (kg) at the time of informed consent * Females must be non-pregnant and non-lactating, and either surgically sterile or post-menopausal * Males must be surgically sterile or, abstinent or, if engaged in sexual relations with a woman of child-bearing potential (WOCBP), the participant or participant's non-pregnant female partner must be using a highly effective contraceptive method * Body mass index (BMI) ≤ 35.0 kg/square meter (m\^2) * Participant must have been diagnosed with essential hypertension for a minimum of 3 months prior to screening * At screening, the participant must have been on a stable regimen of 2 to 3 antihypertensive medications for at least 1 month prior to screening and will be required to maintain this regimen throughout the study, using either an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin II receptor blocker (ARB), as well as 1 or 2 additional antihypertensive medications in the following categories: beta blocker, acebutolol, atenolol, betaxolol, bisoprolol, carvedilol, labetalol, metoprolol, nadolol, nebivolol, propranolol, pindolol, calcium channel blocker or, non-potassium sparing diuretic Exclusion Criteria: * Clinically significant abnormalities in medical history, screening laboratory results, or physical examination that would render the participant unsuitable for inclusion * History of secondary hypertension (HTN) The use of the following at time of screening and during the course of the study: * Other medications for the treatment of HTN (e.g., clonidine, guanfacine, guanabenz, alpha-methyldopa, hydralazine, minoxidil, diazoxide, renin inhibitors) * Medications that may cause hyperkalemia (e.g., cyclosporine or tacrolimus, pentamidine, trimethoprim-sulfamethoxazole, all heparins) * Oral or SC anticoagulants (e.g., warfarin, rivaroxaban, apixaban, heparin, lovenox) * Organic nitrate preparations (e.g., nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, or pentaerythritol) * Phosphodiesterase 5 inhibitors (e.g., sildenafil, tadalafil, vardenafil, avanafil) * Potassium-sparing diuretics (e.g., eplerenone, spironolactone, amiloride, triamterene) Unstable/underlying cardiovascular disease defined as: * Any history of congestive heart failure (New York Heart Association \[NYHA\] class II-IV) * Any history of previous stroke, transient ischemic attack, unstable or stable angina pectoris, or myocardial infarction prior to screening * 12-lead electrocardiogram (ECG) corrected using Fridericia's formula (QTcF) \> 450 milliseconds (msec) in males and \> 470 msec in females at screening, or a history or evidence of long QT syndrome * Any clinically significant active atrial or ventricular arrhythmias * Any history of coronary bypass or percutaneous coronary intervention